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Survival Gu ide
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Survival Guide

ul Gaon Mass MRcP(uK) MRcPcH


ltltd latric Consultant, Israel

''reword by
rofessor Anthony
. .
Milner MD FRCP FRCPCH DCH

lllfofessor of Neonatology, Guy's, King's and


Thomas' School of Medicine, London, UK
:ontents

1. Genetics 1
2. Cardiology 13
3. Respiratory system 37
4. Nephrology 67
5. Neurology 93
6. Gastroenterology 135
7. Endocrinology 169
8 . Haematology 199
9. Immunology 235
10. Metabolic diseases 247
11 . Rheumatology 269
12. Dermatology 285
13. Vision and hearing 303
14. Paediatric syndromes 315
15. Paediatric development 331
16. The long case 339
Bibliography and recommended further reading 343
Index 345
Genetics
1
Genetics questions appear in the examination mainly as pedigrees in the
data interpretation section. A broader knowledge of basic genetic issues is,
however, expected and this reflects the·general importa~ce of this topic in
paediatrics.

CLASSIFICAnON ·OF· CONGENITAL: ABNORMAUnES- .. · ·'t:~'· : ::


A common problem faced by paediatricians is the child with structural
defects. A nom~nclature has arisen to describe the genesis of s,_.ch
deformities. ·· ·
- Malforrruztion: A structural defect resulting from abnormal development;
- Deformation: This is where mechanical outside forces have altered the pre-
viously normal shape of body parts. Examples include oligohydramnios
l~ading to pulmonary hypoplasia and talipes.

- Disruption: An extrinsic force alters a normal fetus usually by a destructive


process (mechanical, vascular or infectious). Examples include amniotic
bands leading to amputations, and congenital rubella.
- Sequenu: When a single error results in a chain or cascade of subsequent
events resulting in a series of abnormalities. Examples include the posteri-
orly placed tongue in Pierre-Robin syndrome that results in micrognathia
and a cleft palate.
- Malformntion syndrome: This occurs when there are multiple structural
defects present that cannot be explained by a sequence (see above).
Examples of this are polydactyly and exomphalos.ln a large number of cases
the cause is not known. Other causes in~lude genetic causes (single/multi-
ple gene effect/chromosomal defects/multifactorial), teratoiens such as
viruses (le~ding to congenital infection), drugs, chemicals and irradiation:
- Association: This refers to cases where there are a number of malforma-
tions present that occur more often together than would be expected by
chance alone. for example VATER/VACTERL and CHARGE syndromes 1
(see Ch.~pter 1-J). In Onl·-tenth of ,,1[ infants with a congenital m,llforma·
tion there will generally be another malformation associated with it. lf
you find one malformation, ,1Iways look for others.

ll.EVELOPMENT AND TERATOGENESIS - ~ "'" . . . .. . ' ~ ·-·'i


The effect of a particular teratogen on the fetus will depend on the nature of
the teratogen and the fetal age, in addition to other factors.

Weeks 1-3
Embryonic stage. At this stage teratogens c1ct in an all or nothing fashion -
either killing the fetus or not affecting it at all.

Weeks 3-10
Organogenesis. This is when organ sy:>tems are the most susceptible to
damage.

Weeks 16-40
Fetal growth and maturation. At this stage unlikely to be teratogenic but may
interfere with growth ~nd physiological functioning of the normally formed
fe tal tissues and organ systems.

Genetic pedigrees routinely come up in the data interpretation part of the


examination a nd you ~hould have a good system for dealing with these
questions. A certain amount of assumed knowledge is expected here such a s
the theory behind the different types of inheritance (found in most paediatric
textbooks).
You must know the commonly used symb(!ls !or.genetic pedigrees (Fig. 1.1 ).

Essential genetic pedigree knowledge


A utosomal recessive (ARl conditions
- The affected individual has two heterozygote (carrier) parents. There is
usually no antecedent history; the disease appears out of the blue.
- 1f both parents are heterozygotes then half the offspring will be carriers, a
q uarter will be affected and a quarter will be nonnal.
-The spontaneous mutation rate for recessive conditions is extremely
low.
-Autosomal recessive conditions and their genes are very rare but the
same recessh·e genes are more likely to be present in the gene pool of
families or smaller races that do not intermarry. Thus consanguineous
relations are more likely to gh·e rise to affected individuals.. This is
because heterozygotes for a particular condition are more likely to come
in contact with each other, producing the abnonnality (homozygous
indi, ·iduals).
2 -The male:female (!vt:F) ratio is 1:1.
Male

Female
0
0
Normal mating

Consanguineous mating
D-0
D-0
db
+
•e Q
Monozygotic twins
Affected male (I)
::::s
Affected female
DizygotiC tw1ns
Do (I)
!:t.
0
en
Heterozygote male for AR conditiOo IJ Numbering of a genetic pedigree


Heterozygote female ()
u
Proband (affected person) .tJ
Deceased 0 "' Proband is 111-1

lg. 1.1 A summary of the main symbols used in genetic pedigrees.

E;romptes include: cystic fibrosis (carrier rate 1/25, one-quarter of


children will be affected so that the incidence in the population is
1 /2500), sickle .cell disease, beta thalassaemia, most inborn errors of
metabolism and spinal muscular atrophy. .

\utosomal doJnant (AD) inheritance


- The condition is inherited from one affected parent.
..... Half of the offspring will be affected and half will be normaL
1- The spontaneous mutation rate is relatively high (compared to autosomal

~
recessive conditions).
Male:female ratio is 1:1.
Compa~ed to AR d~ease, AD disease displays a great deal of variation in
expreSSIOn.
Examples include: hereditary spherocytosis, myotonic dystrophy,

~
retinoblastoma, ruberous sclerosis, Fried reich ataxia and polycystic kidneys.

·linked recessive conditions


-Males are affected. This is because the abnormal gene is on an X
chromosome. Females ha\·e an extra X chromosome to protect them
and therefore only become carriers. whereas males with only another
'empty' Y chromosome are affected. During cell division, however, a
process called lyonisation can occur where there is a random
inactivation of one of the X chromosomes in all the female cells. and
thus some heterozygote females may have some of the features of
the fully expressed X-linked condition ..An example of this is
haemophilia A where female heterozygotes may have prolonged
clotting times. Another example is the raised creatine phosphokinase
(CPK) levels found in heterozygote females in Duchenne muscular
dystrophy.
The lyonisation process that results in an inactin? X chromosome is
also responsible fo r the Barr body seen in ce Hs as a densely stained m as•:
of chromatin within the nuclei (sample cells are most com:eniently taken
from a buccal smear). As a rule the number of B&n bodies seen w ill be
one less than the total n um ber of X chromosomes. Thus normal females
-.2:co will have one Barr body and girls w ith Tu rner syndrome will ha\·e none
- A female carrier parent will result in·half the male offspring being
c:
::J
affected and half the female offspring being carriers.
en - An affected male pa rent w ill result in all the female offspring being
<( carriers and all the male offspring being normal since they inherit the
norma! Y chromosome fro m the father.
E
co
>< X-iinked domina nt conditions
w n .ese conditions a1·e extremely rare. According to the p€digrees affat~d

-(.)
'i:

,.!!!
G>
co
m a les wiU have affected d a ughters and norrtlal sons (d. AD inh.:;;itanct),
Affected fumales pass the condition to hall of their offspring independent ol
their ::;ex. MaieS f)ass the condition on to aU their daughters dfld none of 4!-. :lr
sons. L"' p~ctice Cl number o f these conditions appear io be lethal to m,1lt...1
D. (v.·ho may be stillborn) and thus only femaies a.r e affected. You .should knv~v
a co:;pre oi examp les such as X-linked hypophosphataemic-rickets and incon
tinentia pigmenti (le thal to males).

U$ehli ruie s in deter m inin g ii"~n~-ri~nee patien-• i.-. g enetic


pec:l!Q.g~~&Z» .
1. Count the m:1.rnbers of maies and fema!e:s affected and de termine the M:F
ratio.
- If th~ ratio ~s 1:1 then th e cond ition is likely to be AR o r AD. Smaller
nu:nb~rs of affected ind ividua ls w ill usually be present' in a gent: tic
pec:H~ of AR inheritance.
- If females are affected more common !y !han males t.~i:nk of X-li.'"lked
dom.inim~ inheritance.
- If no furr>a!res are affected think of X-llnked recessive inheritance .
. :i! 1f a."' aff«wd ma le gives r ise to a n affe:ci·~ mal~ trunk o f AD inh~ri t~'"lc.­
(AR <;;;s.; , possible but e xtremely ra re). This is in contrast to X-linked
dominant inhe ritance (affected males never give r ise to an affected
rr.ale). Sometimes it is difficu lt to disr.ng uish betwe-i?n AD a nd X-Iin::...:..d
dominant ill.l)eri tance a n d therefore large pedigrees are m!<:es.. .aty to
de:nonstrate m a le to male transmission (and thus AD inheritanc~).
3. Reme mber that most indi\•idua ls affected by AR ccnditions are w.•1a!iy
sterile or die early.
&ampies ,
In these examp les (as is conunon in the examination) only affected indivtd u
a ls will be indicated (shadecl in) and carriers w ili not be shown. Work ttu:ough
4 these examples '(Fig. 1.2) using the rules abo ve.
+
example~

r-;
:...J :.'l

~ 6 [5
' -(? G)
(!)

0
I


I -,
~ If
0

..r:-~
u inheritance.
---'--1
0

- If asked f o:r ,;\n


:::J
(1)
~
n
en

. 1-.2a This is an example of X·linked dominant


xample, say X·linked dominant hypophosphataemic ricitets rath«r than incontinentia
igmer.ti since the latter is lethal to ma!es.

Exampl&2

+ 6 0 0
6:---+-tJ--,6 rrm
Jllg. 1.2b This ~ an -example .of an X ·Hnlt~ rec.."Ssiva distwl9r.

Example3

Fig. 1..2c This is an example of Af< in'-~ritancE.

Example4

5
Another commonly asked question includes the following:
A couple come for genetic counselling about the risk that their child will
ha\·e cystic fibrosis. The husband's sister has it, but the husband is not
affected and there is no historv in the wife's familv of the disease.
A11swt'r: Cystic fibrosis is inherited as an aut~somal recessive condi·
tion. Therefore since the sister is affected. both her parents must be car-
->co riers. Since the brother is not affected therP. is a two-thirds chance that
the brother is a carrier. We know that the carrier risk in the general pop-
·~ ulation is 1/25. Thus we assume that this is also the wife's risk of being
::::J a carrier.
C/) Therefore the risk of their child being affected is 2/3 (father's risk of
<.. being a earner) multiplied by 1/25 (mother's risk of being a carrier)
multiplied-by 1/4 (risk of child being affected with two carrier parents).
E
co
.n
.0
-You should know about the rare diseases that demonstrate
mitochondrial inheritance. Here we see that some mitochondrial
proteins are encoded. for by the mitochondrial chromosome (rather
:5 than the nuclear genes). Since mitochondria are derived from the
.~
"C mother then these diseases demonstrate maternal inheritance. Male
, (1) and female offspring are equally likely to develop the condition.
co
0. Examples include MELAS and MERRF (see Chapter 10).

CHROMOSOME ANALYSIS ., :..


Thls is another popular data interpretation question. In classic ch,romosomal
. analysis one finds that there are 23 pairs of chromosomes (22 autosomes and
a pair of sex chromosomes). They are sorted by size, position of the
centromere and banding pattern so that the autosomes are labelled from
1-22 and the sex chromosomes are called X andY {see Fig. 1.3). In the top
left hand side are the large chromosomes with median placed centromeres.
· As one passes from left to right the chromosomes become smaller in size
and the centromere moves distally forming progressively more acrocentric
chromosomes. The short arm of the chromosome is called the p arm and the
long arm is ..::all~d the q arm. An older nomenclature divided similar look-
ing chromosomes into seven groups designated A-G + the sex chromosomes-
Patau classification. Genetic testing is most conveniently carried out
using peripheral blood lymphocytes. but almost any tissue may be used.
The chromosomes are arrested in metaphase and stained. In order to diag-
nose tJ:te problem you must label the chromosomes from 1-22 and the sex
chromosomes.

6
xamp les
Example 1

...=...:
'
... ..;.
: :-.,
..·' .:
; ...
~

•<
w .":-=-~ ;'
.... ~
..•
·• ~
""'.... " "I.
;;
' ..
.. 4

.." .. # .-! ..
·v .•" ! " .,• .;

-'
~ I
' 1 \2
-.• .. ' ...
\ 3) 4 I s \ 6

;;;
•!
::
••
- ~

3:
~

; :;
-=.
'~• ..,,.]
~
,;, '9 '' '
~ ~ ! '!I ~

\
7
~
:; ;;
'§ ~
iS
... &
s:t
I
.'i
""
10
;:r,::;
' 1~
~{ ~~
-"
::1 •
12

i""-.
~ !!
I
13 ' .. '
!I !!
14. ... 15'
!l '
16
!I!!
....
17
•1&•
'!! -

.. .
~ •.
~ ! ~:: 'I
"'" ;;. "5
R ~~
"'' .3
""'
••
19
••
20 21 22
i
~
Cl
X y

f ig. 1.3a If there is one lone X chromosome then tht! individual has Turner syndrome.

Example 2

,..
.-" .. ..
-~
:.:;, •'
., ff :; ; ;
.:;r ~

:: ..
..,,
5
.. ..... .7
; ;j '
~ •
-
.." •..... "'" .. • ~ ".. ~

' J
' ' 2 3 " 4
I
'' 5

s .• ~
..
i ..
!!
;;
j/
• 9..
...--.... ~:!
;i :i
• 7 8 •• 10
•' 11
;j:. - ::= _j aJ
w::
!I '!!.
•13• .. i
Q
~ !l
'II
j ::1

i I!..
'0 •~ •"
14 15 16 17

i .,.=
•.

...; •;[
$'1 ~ ; A 3 :l
.:r ~ :< ,;
".. ""J
•• 19
•"20" 21 22
!!

•..
:; ;
~

Pig. 1.3b If t here is an extra chromosome at chromosome pair number 18 then the
'' X y

Individual has Edward syndrom!!.

7
Example 3

. . ....
,. ..,, \{,, \\
,;;- ~ ~ ;
Q) ';1 ; ~
~ ~ ~~
:2
:s 5 6
C) 3 4

ns .Ss
::; i ss
::1;
Qf}
:r q )}
> i\
, !J
i i
·~ ( 9' ••
-.
10 11 12
:s
0
ct
E
.. ;
J§~
15
el t'I S
.a~ .
f!fl
16
" ..~~;
17

ns .~:~e::~ Q
~-i
~
i1
21 IS
u
·.:
.... '
X y

."C~ Fig. 1.3c This shows an extra chrom osome at position 21. This is trisomy 21 (Down
syndrome).
Q)
ns
0.
Example4

0. C\
::; Q
;;r ~
!!~

4 5 '' 6


.
. ; ~..
9
!{
• • 10
...
{(
11
If
#;;J

..
.a a
12
..
el

14
~~
go~
...
15
.. l.. l
16
. I(

18
s
/i
19 20 21 22
X y
Fig. 1.3d If there is an extra X chromosome (in addition to the normal male X and Y)
then the individual has Klinefelter syndrome.

CHROMOSOMAL NOMENCLATURE . · · · . . .. . ,
You will be expected to express karyotypes in the conventional way (Paris
8 nomenclature ).
First you mention the total number of chromosomes, then you mention the ·
sex chromosome constitution and finally the genetic abnormality.
~ormal: -!6 XX.
Tumer syndroll!e: 45 XO.
KJinefelter syndf?tne: 47 XXY.
Cri du chat syndrome: 46 XY, del (p5).
46 XY, t(5;10)(pl3;q25). This is a balanced translocation between chromo-
somes 5 and 10 at the break points indicated in brackets at the end. ·

SPEOFIC EXAMPLES OF GENETIC TOPICS . .".


Down syndrome
Since Down syndrome is so common you must know about its inheritance in
detail. The typical phenotypic description is found in Chapter 14.
The risk of Down syndrome and most chromosomal abnormalities
Increases with increasing maternal age (increasing the non-disjunctjon type of
Inheritance). At the maternal age of 20 the corresponding risk is 1:2000, at age
30 1:700, at age 40 1:100 and at age 45 1:50. Sixty per cent of first trimester
apontaneous abortions are secondary to chromosomal abnormalities. This
figure falls to about 0.5"/o of. all live births.

Inheritance of Down syndrome


In 95-97% of caSes the cause is non-disjunction during the first meiotic divi-
lion. The result of this is a.n extra 21 chromosome in all body cells. The recur-
rence rate for non-disjunction is 1%.
In about 2-=-3% of cases a translocation is responsible for the condition.
A translocation is the transfer of chromosomal material between two or more
homologous chromosomes which is usually reciprocal in nature: that is, an
c!lcchange of genetic material. In this case the total genetic material in the per-
IOn is complete (in other words balanced, none having been lost).
A Robertsoruan translocation describes the particular case when the long
anns of hvo acrocentric chromosomes (chromosomes with centromeres dose
to one end: that is, chromosome numbers 13, 14, 15, 21 and 22) fuse at their
centromeres. Since both chromosomes have fusep., the total complement of
chromosomes will be 45; however si.r,tce the total genetic make-up is unaltered
(balanced) the person will be phenotypically normal. A balanced transloca-
tion carrier may give rise to chromosomaUy unbalanced offspring.
If a child has a~- unbalanced translocation giving rise to Down syndrome
there is a 25% risk that the parent has a balanced Robertsonian translocation
(most commonly between chromosomes 14 and 21) and a 75% risk that it is
1 de novo translocation. This is the reason why when a baby is born with
Down syndrome secondary to a translocation, a karyotype of both parents is
needed.
It is worthwhile working through an example of the patemal/matemal
bAlanced Robertsonian translocation carrier. During gametogenesis five types
of gametes can be formed (see Fig. 1.4). You will see that the chances of a
l~wn syndrome baby is 1:4 but the monosomy 21 fetuses abort so that the ::9
!'
I
II Q)

II
:2
::::s
(!)
I Normal Balanced Robertsonian translocation
(45 xxt(21,14))
I "'
.2: Potential gametes
I c:
::::s
<f)
<(
..
E
w
"'
)(

-0
·c
-~
"C
Q,)

"'
D.. Normal Monosomics
die
Down
461(21,14)
Balanced Robertsonian
translocation

Fig. 1 •.4 A genetic description of how a Down syndr.ome translocation may occur.

risk is actually 1:3. However a large' number of Down syndrome babies abort
naturally so the risk falls to 1:10 or 10% in carrier mothers. The risk is 2% in
carrier fathers (lower than in female carriers due to sperm immotility). It is
impossible to distinguish benveen the non-disjunction type and translocation
type solely on phenotype.
The last possibility is mosaicism occurring in about 1% of cases: here some
of the cells display trisomy 21 and others do not. Phenotypically these chil-
dren are usually affected to a lesser degree, as compared to those derived
from non-disjunction or translocation types.

Maternal serum alphafetoprotein (AFP)


Know a little about maternal serum AFP. It is taken at about 16.-18 weeks of
pregnancy. High AFP levels are associated with neural tube defects (80%
detection rate). It is also associated with multiple pregnancies, abdominal
wall defects, Turner syndrome and intrauterine death. Low levels are·associ-
ated with Down syndrome. In addition the triple test w hich uses two other
maternal serum markers (hCG - high. and unconjugated oestriol - low) has
increased the detection rate to about 60"~ with about a S'Y., false positive rate
(compared to 20"'.. with serum AFP alone). The ratio gives the mother a risk
10 (though not a certainty) of ha,:ing a child with Down syndrome.
!Stic fibrosis
e genetic defect responsible for cystic fibrosis is located on chromosome 7q
e ng arm). It encodes tor a membrane protein responsible for chloride trans-
oct called cystic fibrosis transmembrane regulator (CFTR}. It functions via
MP. The gene is large and many mutations (more than 200) have been
escribed that result in the disease. The commonest mutation is a three base
air deletion (and subsequently a single a'mino acid deletion- phenylalaiune)
t position delta FS08, occurring in about 70% of individuals in Euro·pe and
Uorth America (however this prevalence varies with different racial groups•
.g. Ashkenazi Jews- approximately 20%). Approx.imately two-thirds of indi-
iduals with cystic fibrosis appear to be homozygous and one-third het-
rozygous for the mutation. In the heterozygotes the delta F508 mutation will
e paired w ith another mutant allele for the CFTR. Using genetic analysis via
!horionic villus sampling (8-10 weeks) and amniocentesis (16-18 weeks)
ntenatal diagnosis is possible (see ~apter 3).

I U<hOdne muscular dystrophy

l
~e defective gene has been located to the X chromosome and it is very large
ndeed, accounting for of its size. There is a very high ratio of intron (non-
1%
!:oding) regions to exon (coding) regions. The protein usually encoded for by
this gene is called dY-strophi.n and its deficiency results in the disease.
Spontaneous. mutations have been noted in about one-third· of cases. DNA
analysis detection techniques haVe enabled us to detect carriers and affected
Individuals, thus allowing antenatal diagnosis. Males are affected, but
because of lyonisation some of the muscle cells in carrier females will contain
the abnormal allele and result in release of CPK resulting in levels out'side the
normal range in some female carriers.

Angelman syndrome and Prader-Willi syndro~e


These two conditions have led to the concept of genomic imprinting (see
Chapter 14 for phenotypic descriptions). Genomic imprinting describes the
Influence of parental chromosome origin on the expression of a particular
1ene. Both Prader-Willi syndrome and Angelman syndrome may be the
result of a deletion in the long arm of chromosome 15 (·1 5 q 11-13). If this
chromosome is maternally derived then Angelman syndrome results, but
If lt is paternally derived theJ;t Prader-Willi results. It has been found that
If both 15 chromosomes are derived from the mother then Prader-Willi
phenotype will occur (and conversely if both are derived from the father
then Angelman syndrome will occur). This is called uniparental disomy
•nd it thus seems that the lack of a paternally derived 15 q 11-13 will result
In the ·Prader-Willi phenotype (and the lack of a maternally derived 15 q
11-13 will result in Angelman syndrome). The explanation above describes
1bout half the cases of Angelman and Prader-Willi syndromes and
th~ remainder will have either normal karyotypes or other genetic
• bnormali ties. 11
Fragile X syndrome
Fragile X is the most common inheritable type of mental retardation in mall
accounting for about 30% of the total number of cases. It also causes 10% 1
mild mental retardation in fumales (heterozygotes}. A chromosome m arki
called the fragile X site can be seen at the end of the long arm of the X chrom1
some when the chromosomes are incubated in a folate deficient medium. n
carrier frequency in females is about 1:1000. The fragile site is only a mark1
and not reliable in all cases. The fragile X gene has been identified as an ove
amplified section of DNA with various lengths of CGG repeats (see Chaptt
1-! for phenotypic description).

Genetic anticipation
This describes the case where the severity of the inheritable disease increaS('
with each subsequent generation. It has been noted that in a number of thes
conditions !here is a greater frequency of trinw::leotide repea ts than on 1
would nonnally expect. The diseases that demonstrate sue~ .1 1 1ticipati01 1
include Huntington chorea, myotonic dystrophy and fragile ~,syndrome.

12
,[ardiology
2
FETAL CARDIOVASCULAR PHYSIOLOGY : · .. . .· ·.
'l'he 'basic science' nature of this topic - as well as the potential pathological
1 Implications in paediatric cardiology- makes it a likely viva question.
Oxygenated blood from the pla centa retums to the fetus via the umbilical
vein (of which there is only one ). Fifty per cent traverses the liver and the
remaining 50% bypasses the liver via the ductus venosus into the inferior
vena cava. In the right atrium blood arriving from the upper body from the
I'Uperior vena cava. (low oxygen saturation) preferentially crosses the tricus-
pid valve into--the right ventricle and then via the d,.uctus flows into the
1lescending aorta and back to the placenta via the umbilical arteries (two) to
reoxygenate. The relatively oxygenated blood from the-inferior vena cava,
however, preferentially crosses the foramen ovale into the left atrium and left
ventricle to be distributed to the upper body (including the brain and coro-
nary circulation). Because of this pattern of flow in the right atrium we have
highly oxygenated blood reaching the brain and deoxygenated blood reach-
Ing the placenta. High pulmonary arteriolar pressure ensures that most blood
traverses the pulmonary artery via the ductus.

Changes at birth
t. Occlusion of the umbilical cord removes the low-resistance capillary bed
from the circulation.
1. Breathing results in a marked decrease in pulmonary vascular resistance.
) In consequence, there is increased pulmonary blood flow returning to the
left atrium causing the foramen ovale to close.
4. Well-oxygenated blood from the lungs and the loss of endogenous
prostaglandins from the placenta result in closure of the ductus
arteriosus. .

CONGENITAL HEART DISEASE .. · · ·


Yuu should know the approximate incidence of congenital heart disease
w hich is approximately 8/1000 live births. 13
Ventricular septal defect- 30% Coarctation of the aorta - 6%
Patent ductus arteriosus- 8% Aortic stenosis - 6%
Pulmonary stenosis - 8% Transposition of the great vesSels:.:.. 4%
Atrial septal defect - 8% Atrioventricular septal defect - -l'Y~
Tetralogy of Fallot- 6%
It is important to be familiar with what lesion is likely to present when, since
->cu this will b~ vital when ans":ering a possible clinical scenario in the written or
clinical e xaminations.
·~ f I

::s Cardiovascular lesion chronology


en -Within tile fir$t few hours: pulmonary or aortic atresia/critical stenosis,
<(
.. hypoplastic left heart syndrome.
E
cu
- Witlzi11 tire first fi•w dnys: transposition of the great arteries, tetralogy of
>< Fallot, hypoplastic left heart syndrome, patent ductus arteriosw. (PDA) in
w small p~ma ture infants.

-
u
'i:
.!2
'C
Cl)
l'G
- Within tire first few weeks: critical aortic stenosis, coarctation of th.: aorta.
- W ithi1i tlze first few months: any of the left to right CL-R) shw1!., (caused by
falling pulm~nary vascular resistance).

fl. Presentation of congenital cardiovascular disease.


A useful way at looking at congenital heart disease (CHD) and its presenta·
tion is to divide it up into three categories. These are of course simplifications
but nevertheless useful.

1. Those that are ductal dependent for pulmonary blood flow or mixing
Main presenting clinical feature is cyanosis.
Decreased pulmonary bloodjlow:·pulmonary stenosis, pulmonary atresia ±
ventricular septal defect, Ebstein anomaly, tetralogy of Fallot, single ven-
~de or double outlet right ventricle with pulmonary stenosis.
increased pulmonary blood jloru: transposition without significant mixing.

2. Those that are ductal dependent for systemic blood flow


Main presenting clinical features are those of systemic hypoperfusion
(decreased peripheral perfusion, reduced urine output. metabolic acido-
sis). Remember that the important differential diagnosis of this type wiU be
neonatal sepsis or a metabolic disorder.
: Examples: coarctation of the aorta. interruption of the aortic arch, critical
aortic stenosis, hypoplastic left heart. There are of course non-ductal
dependent cardiac causes of systemic hypoperfusion such as cardiomy-
opathy, myocarditis and supraventricular tachycardia (SVT).

3. Those that are unlikely to be ductal dependent


The main presenting clinical feature will be rrspiratory distress and
increased shadowing on the chest X-ray (CXR). Examples:
Mi.Ting lesion: total anomalous pulmonary venous drainage (fAPVD)
with no obstruction and adequate foramen ovale. tnmcus arteriosus,
14 single ventricle without pulmonary stenosiS.
Table 2.1 Cardiac catheter
Normal values
0 1 saturation Pressure (mmHg)
Vena cava (VC) 75% o-s (')
Right atrium (RA) ,·, 75% m=3 I»
Right ventricle (RV) .. 75% 2513 0.·
Pulmonary artery (PA)
Left atrium (LA)
75%
98%
2518
maS
o· ·
Left ventricle (LV) 11018
0
~
98%
Aorta 98% 110165

Left to right lesic>~ts: patent ductus arteriosus, ventricular septal


I- defect, atrioventricular canal defect.

U !ii•lf;i4iWiWjN;·I·t.1411M I - ···-
( ardiac catheter data is still a popular topic for, the Part 2 examination. In
l•rder to attempt any of these questions it is of course vital to know the nor-
~ nal values of pressure and saturation in the various chambers of the heart
nd the major vessels (see Table 2.1)
The way of attempting these types of question is to follow the pressures and
saturationS around the heart (through the great vessels and chambers) sys-
tematically noting any deviations from the normal valu~ (Table 2. 1) and
noting any unexpected step-ups or step-downs in saturation or pressure.
ln a·left to right or right to left shunt the exact point of the step-up or step-
down in oxygen saturation (in the right or left sides of the heart respec-
tively) indicates the level of the shunt-
A higher than expected pressure in a chamber or vessel can be expla~ed
by a stenosis ahead of it, by a shunt such as a left to right shunt (tow~
the chamber or vessel) or simply by a backlog of pressure.
A drop in pressure between a ventricle and an artery implies a stenosis in
the artery.
Equal ventricular pressures may be due to a large ventricular septal defect
(VSD}, Eisenmenger syndrome, common arterial trunk and tetralogy of Fallot.
l.tt us now go through the lesions that are likely to come up in the examinatioll.

0 2 saturation Pressure
RA 88"/o 5
RV 87% 35/5
PA 87% 35/12
LA 97"/o 6
LV 97% 100/8
Aorta 97"!., Hl0/58 15
s.
This is the result of an atrial septal defect (ASD). There is a rise in saturatio1
going from the vena cava (not given!) to the right atrium. This can also bt
caused by TAPVD where blood from the pulmonary veins drains directly o:
Q)
indirectly into the ·right atrium. This is rare and you should remember tN
"C this lesion can be cardiac, supracardiac or infracardiac, the last type beinf
:::s associated with obstruction.
(!)
2. Oz saturation Pressure
C'G
.~ svc 75%
~
:::s
U)
<(
RA
RV
PA
LA
75%
75%
88%
95%
3
35/5
35/14
8
"'
lh
lr;

E LV 95% 100/8 ll
C'G Aorta 95% 100/55
)(
w There is a step-up in saturation and pres.c;ure betw·een the right ventriclt

-
(J
·.:
."C~
Q)
C'G
and the pulmonary artery. This is an e).~ •.• 1 ·le of a patent ductus arteriosw
(PDA).
3.
SVC
Oz saturation
68%
Pressure

~
0..
IVC 64%
RA 72% u
RV 84% 85/7 I!
PA
LA
85%
98%
20/8
10/5

LV
Aorta
91%
88%
90/5 .
90/55
There is a step-up in oxygen saturati~n between 1he ·right atrium and right
I
ventricle implying a left to right shunt at the level of the ventricles. The pres·
sures also show a step-up at the same level. This is the pattern one would t
expect with a VSD. However, in addition to this we notice a step-down in
pressure from the right v~ntricle to the pulmonary artery and this i:rhplies a
stenosis. We also notice a desaturation as we pass through the left side of the
heart and the low saturation in the systemic circulation (aorta). These-addi-
tional features make the diagnosis tetralogy of Fallot.
4. ol saturation Pressure
LA 98% 10/5
LV 98% 152/60
Aorta 98% 90/50
There is dearly a higher pressure than we would expect 'in the left ventricle
for a paediatric patient and we also see a step-down in pressure between 1he
left ventricle and the aorta implying that this is a coarctation of-the aorta.
The commonest site is just distal to the left subclavian artery.

16
0 2 saturation Pressure
VC 30%
RA 32%
RV 32% 90/10
PA 92% 6/J/7 0

LA
LV
93%
94%
7
6/J/7
a.c;·
Aorta 35% 88/6/J 0
ca
We-an see here that the pressures and satuntions in the pulmonary artery '<
IJid aorta match those of the left ventricle and right ventricle respectively:
that· is, the revetSe to what we would expect in practice. The diagnosis is
transposition of the great arteries.
6; 0 2 saturation Pressure
RA 65%
RV 65% 90/10
PA 68% 100/6/J
LA 95%
LV 82% 100/12
Aorta 83% 100/55
Here we can see high pulmonary pressures which can be caused by large VSD
or AV canal defects.which if present for long periods result in irreversible pul-
monary hypertension and reverse right to left shunting· - Eisenmenger
tyndron*. .
... . --
., ....
CYANOSIS AND THE HYPEROXIC TEST· (NITROGEN WASHO~T ,
TEST) "_· : .' , _'>. . <,,,,~ ;i~ . .:.,. _. ..
..
lhis is a common topic and "you should be familiar with the theory. This is
e useful test to help to distinguish between cardiac and respiratory disease
causing cyanosis in a baby. An arterial blood gas is taken (preductal) and
~peated after breathing 100% oxygen for 10-15 min. A P02 of less than
20 kPa (usually less than 10 kPa) is suggestive of a fixed right to left shunt
(which implies a lesion in which there can be no increase in pulmonary
llood flow or mixing of systemic and pulmonary circulations, e.g. tetralogy
of Fallot) or severe pulmonary hypertension. A Pa02 of more than 25-30 kPa
definitely excludes it as the cause of cyanosis. In this case one would have
to consider lung pathology, large left to right shunts .causing pulmonary
oedema and patients with mixing of their pulmonary and systemic circula-
lions. Lung pathology is also more likely if there is a raised PC02 in the
blood gas.
Remember the potential danger posed to the patient by the test if they are
dependent ·on maintaining left to right mixing through a patent ductus arteria,.
IUS (PDA, e.g. in aitical pulmonary stenosis). 1be oxygen may stimulate the
duct to close. Prostaglandin PGEl should be available during the procedure.
I •
Example I
A baby is cyanose d. He is given 100% oxygen to breathe for 15 min. The fol
lowing results are obtained .
FiO: P01 PC01 PI
f\ir 7.8 5.2
100% 0~ 17.1 5.7
This implies a right to left shunt type of congenital heart disease: the diniciar
would go down the cardio,•ascular route of investigation and treatment.
Remember that in ~ddition to cardiac and respiratory causes of centra'
cyanosis there may be other causes to consider: central depression includint (
fits, polycythaemia and methaemoglobinaemia.
There are questions describing a well baby who appears cyanosed withoul •
obvious respiratory or cardiac disease and who has a normal hyperoxic test
Furthermore the blood remains a brownish colour after breathing oxygen •
One must then think of methaemogiobinaemia as a cause and one would per·
form a methaemoglobin concentration and investigate a reason for it (set
Chapter 8 for details of methaemoglobinaemia).
You should know that cyanosis appears when arterial blood contains mon
than 5 g per cent of deoxygenated haemoglobin. In polycythaeinia cyanosis is
common because of the large amount of haemoglobin in the blood and rare il1
anaemia' because it is difficult to produce a sufficient amount of deoxygenat·
ed haemoglobin to produce cyanosis (even though tissue hypoxia is more
likely in anaemia}. Peripheral cyanosis can be the result of amral cyanotic
causes as well as reduced blood flow to the skin (e.g. vasoconstriction caused
by the cold) because of oxygen extraction.

These come up frequently and you :s~ld 'be familiar with the general rules
relating to paediatric ECGs and the common patterns. Approach this in·a sys·
tematic way.

Normal axis
This will vary according to the age of the child. At birth ~een +60 to +180
(approx. +80 by 1 month of age), at 1 year +10 to +100 and at 10 years of age
+30 to +90".

Pwave .
• Re~ber that 1 mm on an ECG is equal to 0.04 sand 10 mm in
. amplitude equals 1 mv. ··
• P waves should always precede a QRS complex in sinus rhythm. Sinus
arrhythmia is very common in children.
• P waves should ~e positive in 1.11 and aVF. P waves should be less than
2.5mm.
• Right atrial hypertrophy /enlargement: P wave in lead 11 > 2.5 mm
18 (P pulmonale).
• Left atrial hypertrophy I enlargement: bifid P wave (P mitrale) usually
> 0.09 s.
J
PR interval
Measured from the start of the P wave until the start of the QRS complex. This 0

is usually between three and fh-·e small squares (0.12 and 0.2 s). This will be
reduced in Wolff-Parkinson-White syndrome and prolonged in first, second
a.o·
and third degree heart block. 0
cc
'<
QRS complex
• Look in tum at.the duration, presence of Q waves, hypertrophy and QRS
progression.
• Duration is normally up to three small squares (0.12 s). Abnormal Q
waves are more than 4 mm deep. However Q waves can be normal in
11,111, aVF, VS and V6. Abnormal Q waves can be seen in ischaemia and
hypertrophic cardiomyopathy.
• There are criteria that you should know for the diagnosis of right and left
ventricular hypertrophy:
In right ventricular hypertrophy < 3/12: R wave in Vl > 15 mm at all
ages.
. > 3/12: R wave in VI > 10 mm.
In addition o~e would expect RAD > tso•. . .
• In left ventricUlar hypertrophy the Rwave iri V6 < 3/12 > 20 mm.
> 3/12 < 25 nun.

QRS progression
There is a gradual change from right ventricular dominance to left ventri-
cular dominance as the child grows up (see Fig. 2.1). Any deviation from the

Vl V6

1) Newborn Righi ventricular dominance

2) 1 month onwards

3) 3 years onwardS

fig. 2.1 QRS progression throughout childhood. 19


normal patterns shown here away from those appropriate for the age toward
(1) or (3) indicates either right or left v~ntricular hypertrophy respectively.
Bundle branch block (BBB) is indicated by a prolongation of the QRS corn
plex (> 0.12 s). In right BBB the rules of M pattern in Vl (RSR pattern) and\\
pattern in V6 (with slurred S wave) apply (MarroW). In LBBB there is a W pal
tern in Vl and M pattern in V6 (WilliaM).

-~ QT interval
·~ This is measured fr.~m the beginning of the qRS complex to,~e end of the 1
::s wave, and is usually between 0.35 and 0.45 s. It varies with rate and yo1
0
<( should therefore refer to QT tables in order to be accurate.
Increased QT interval is seen in congenital long QT syndromes, fo
E example in Jervell-Lange-Nielsen syndrome '(associated with sensorineura
ca
)( deafness) and Romano-Ward syndrome. These syndromes may be asso
w cia ted with sudden death. The QT interval may also be increased in hypo

-
0
·c
.!!!
'C
Cl)
C'CI
calcaemia, hypomagnesaemia, hypothermia, hypothyroid ism , severt
rheumatic carditis and with· drugs such as amiodarone, quinidine and
tricyclic antidepressants.

0.. Twaves
'f waves are upright irl Vl at birth. T waves in Vl then invert by the end of th!
flrst week but become upright again by puberty. T waves are always uprigh
in V6 and if they are inverted one .must consider a myocarditis or possibl)
cardiomyopathy.
You must know the following patterns since they come up regularly: 5e(
Fig. 2.2 for some common examples,

Heart block
There is a prolonged PR interval (> 0.2 s). Called first degree if the P wav(
is always followed b...y a QRS complex and second degree if the P wave ii
not always followed by a QRS complex. This latter group is called
Mobitz type 1 (Wenckebach) if the PR interval gradually increases in
length until there is a dropped beat and Mobitz type 2 if there is a fixed P~
interval where dropped beats are regular (e.g. 2:1 or 3:1). This type is mo~
likely to progress _to complete heart block (CHB) and thus has a wors~
prognosis.
Third degree heart block (see CHB above) displays no relationship
between P and QRS complexes and there is a ventricular rate of aboul
30/min. Neonatal CHB is associated with maternal SLE with anti-Ro antibodiei
and can alSo be associated with-cardiac surgery. P waves are not conducted
to the ventricles and there is a spontaJ\eous escape rhythm (approximately
30/min). There may also be pacing. spikes superimposed on the ECC.
Clinically there may be a variable first heart sound and the presence of giant
A waves (cannon wa,·es) on the JVP (also seen in ventricular tachycardia
and nodal tachycardia) as a result of atrial contraction against dosed AV
"20 valves.
.:;: :::..tLtrXdl/\1\~AL,~
Ar-cri"A/J
• :
::..;. ::
1 Atrial ttuner wilh 4:1 block


~
: , . ! . : .
~
. .
~
.v . h
; 1
(")
: : ' • • 0 •


a
0
2 Complete (3rd degree) heart bicct<
0
• I ~ J ! UJ
'<
1

1
4 Wotff-Pari<inson-White syndrome

i interval ..
I '
.
I"
! I L._rJH. 'I-"'"--.:.'~·
1 I
5 Atrial septal defect - ostium secundum with right axis deviation and
incomplete right bundle branch block
I ·l aVF v~ V6
!: I

ll i
.., n.
,~ D'
\IF" 1- l- N ~ 1'-
M ~""" i- - !"llj''- ~

I. I
' I !
.'

l '
Ptl• 2.2 Some common examples of ~~iatric ECG ~uestions. ~1

v\
Right bundle branch block and left bundle branch block
Remember Marrow and William patterns. An incomplete bundle bra~d
block occurs when the QRS complex is less than 0.12 s but fearu.:res of Marr.m
and William (see above) are present.
Q)

·-
"0
Dextrocardia
Inverted P wave in lead 1, upright in a VF and loss of normal QRS progressio
--
"'>
as one goes from Vl to V6. -·- --~ _ . ___ · · ·-

·~ Wolff-Parkinson-White syndrome
:::s Delta wave (slurred upstroke of the QRS complex) and shortened PR. mt~T"Jal
en Predisposes to paroxysmal SVT. '
c(
.. Amal flutter and atrial fibrillation
E In atrial flutter there is a saw tooth pattern with an atrial rate-of appro~!el)
"'><
w 300. There is usually a 2:1 block giving a ventricular response of 150/rrun. Th

-u
'i:

,
.•!!! -
Q)
co
degree of AV block can be increased with' vagal manoeuvres. In atrial fiirrill
tion there is chaotic atrial activity giving rise to an irregular ventricula
response and .therefore an irregular Q~ intenral and irregular baseline. .
. The commonest causes of these types of arrhythmia..are-post-surgical-(e.g
post-ASD repair), CHD (e.g. Ebstein anomaly), disease resulting in dU~
a. atria and myocarditis.

Left and right ventricular hypertrophy .


Right ventricular hypertrophy ·is caused by left to right 'iliunts (e.g. VSD,I
ASD, ~DA), right.~~tricular .outfl9w tra~ _obstructioJ'\J~ch as puL7.onary'
at!'esia or stenosis} and cor pulmonale. Left ventricular hypertrophy is cau5€d 1
by left outflow tract obstruction (aortic stenosis or coarctation), ASD (ostium
p rimum defe<:t), VSD, PDA and tricuspid atresia.

Ventricular tachycardia
A wide complex regular tachycardia. A BBB with SVT is another cause of a
b road complex tachycardia. They can be distinguished by: (a) the preso:nce 01
absence of cannon waves (seen in VT); (b) the effect of earoticfsinus massage
(no effect·in VT); (c) Vf more likely in older patient with history of heart dis·
e ase; (d) in BBB the QRS complexes look the same in SVT as when in nonnat
rhythm whereas the o ld ECG in VT usually shows norll\.al QRS complexes:
(e) the rhythm in VT is very regular; (f) LAD is commoner in VT; (g) QR!:
> 150 ms is more likely to be a result of VT; (h) evidence of AV dissociation·
independent P wave5, fusion or capture beats (in VI). ·

Left axis deviation in a neonate


This is found in; (a) atrioventricular septal defect; (b) tricuspid atrsia; an<
(c) pulmonary stenosis in Noonan syndrome.

ASD
- Ostium prinmm: left axis deviation and right bundle branch block.
- Ostium secundum: right axis deviation and right bundle b ranch btock,
·22 usually incomplete.
pothennia
~(
pothermia can cause bradycardia: J waves seen as a hump on the descend-
!'\ limb of the QRS complex, increased QT interval and ventricular fibrilla-
n. Beware of the shivering artefact on the ECG.

tctrolyte imbalance
HypokJJlaemia causes prolongation of the PR interval, ST depression,
.s·
0
Q)

c.
T depression/ inversion, prominent U wave. _,
•HyperkJJiae;nia firstly produces peaking of the T waves which is followed 0
cc
, by loss of P waves and then P.~olongation of the QRS complexes. '<
1
a Hypocalcaemia prodt,tces prolosjgatio~·of tl_\~.QT interval and
hypercalcaemia causes shortening of the Qr interval.

el) crease in the PR interval


may be caused by hypokalaemia, myocarditis, rheumatic fever, ASD,
J tein anomaly, ischaemia, hypoxia and digoxin therapy. A decreased PR
rval is seen in Wolff-Parkinson-White syndrome and the Lown-
ong-Lev ine syndrome.

oxin
ou should be familiar with the effects of digoxin on the ECG. A common
1\ange seen in children on digoxin is a prolonged PR interval and 'reversed
lick' ST segment depression. Cardiac toxicity may p,roduce any arrhythmia,
·D•nd ventricUlar bigeminy (alternating ventricular extrasystole and normal
iiJ ventricular ~omplex> is one ot the commoner·abnormalities. toxicity is made
etlnore likely with hypokalaemia. ·
IIr1

11\ls is an important area for potentid qu~tions throughout the exam. Here
·a are some of the more common ones. ·
OJ
't
~ Jlalod<-"Taus s ig {BT) shunt
al 1'hi.s is the commonest palliative shunting procedure used in conditions
s. where there is a severe reduction in pulmonar.y blood flow: for example, pui-
S monary atresia, tetralogy of FaUot. The classic type involves connecting the
l• aubdavian artery to the ipsilateral pulmonary artery. The modified type uses
" Teflon tube graft between the two arteries (usually right sided).
Occasionally a child may become recyanosed some time after the procedure.
lbcclude a blocked shunt with a V/Q scan which will demonstrate reduced
lung perfusion.

llashkind procedure
11\is is the balloon atrial septostomy that can be used as an emergency meas-
IIN to produce mixing in the cases of tricuspid atresia and TOGA. It is per-
formed during cardiac catheterisation. ·'~.
TOGA procedures r
The Jatene operation involves the switch operation where there is reimplan
tation of the coronary arteries and swapping the pulmonary artery and aor~ ·
to their proper positions. The Senning and Mustard operations use intra-atrir
baffles to redirect blood along more anatomical routes (the Senning operatiO:
uses less foreign material than the Mustard).

Fontan procedure
This D"!yolves the connection between systemic venous vessel~ and chambe~
(IVC, SVC and right atrium) t~ the pulmonary artmes. This therefore bypas!
es the right ventricle. This can be used for tricuspid atresia. smgle ventricl
· anatomy and pulmonary atresia. It requires a normal pulmonary artery p~
sure as well as adequate size of the pulmonary artery. Complications includ
right heart failure including peri-:ardial and pleural effusions, sick sinus syt
drome and other arrhythmias.

Norwood procedure lu
This is used for hypoplastic left heart syndrome. It is a two-stage procedllll'
which essentially links the right ventricle to the aorta. The pulmonaty arte1
is divided and the proximal segment is linked to the ascendL'lg aorta and tl
distal segment to the descending aorta via a Blalock-Taussig shunt. An atri
septectomy produces continuity between both atria. Thus blood is pump(
from the right ventricle into the aorta via the pulmonary valve with pu
monary blood flow supplied by the systemic to pulmonary shunt: Stage
involves the Fontan procedure. An · alternative treatment involves card~
transplantation at birth.

-All the left to right shunts usually give rue to a large heart, large puh!~O:ull
artery and plethoric lung fields. Beware of ~onf...tsing cardiomegaly with U
normal thymus gland in the neonate (sail sign): ·
-Aortic stenosis may give a prominent left ventricle and post-stenotic dilal
tion of the aorta.
- Coorctaticm _of tl!c aorta may give rise to a promirtent left ventricle al)d po
sibly rib-notching caused by erosion of the undersurface of. the ribs_by c(
lateral cirCulation (seen in children over the age of 4 or 5 years).
-Pulmonary stenosis may give rise to post-stenotic dilatation of the pt
monary arte:ry.
- Tetralogy of Fallot gives rise to the boot-shaped heart with the apex abO'
the left diaphragm and a concave left heart border ·and small pulinona
artery with oligaemic lung fields.
- Transposition of the great arteries gives rise to the egg-<>n-side appeara111
!24 This is caused by a narrow base since the great vessels are superimp<»
rather than side by side and also as a result of the absence of the main pul·
1
monary artery segment arising from its usual location.
\ f()tpl anomalouspulmonary venous drainage: There is a small heart with
1 Increased pulmonary vascularity and venous congestion. In the infracar-
(")
} diac types that are associated with obstruction there may be extensive - I»
•had owing and even a total white out which can often be misdiagnosed as
lung disease (especially confused with RDS and group B streptococcal
a

pneumonia) caused by an increase in interstitial fluid. 0
cc
~ Ebstein anomaly: X-ray shows a very large heart and reduced pulmonary '<
perfusion. The other main cause of a massive heart is cardiomyopathy.
~ Pulmonary hypertension: Peripheral pulmonary markings are lost (pul-
monary pruning~.

Aa ln clinical paediatrics, pattern recognition plays a v ital role and the fol-
lnwtng are some examples that you should be familiar with for the data inter-
~J•nttation, grey cases and viva.

~ After the first few weeks of life, a baby is now having difficulty complet-
ing feeds, has failure to thrive or excessive weight gain(> 25-30 g/day),
ltWe~ting, tachypnoea post feeds, irritability, cyanosis or recurrent chest
infections. Heart failure should be in your differential diagnosis.
Do not-forget hypertensive encephalopathy in a child who is fitting or in a
coma. There will usually be papilloedema and possibly retinal haemor-
rhages. In the clinical history there may be evidence of a cause: for exam~
ple, the child having had proteinuria 3+ which was not picked up 8 months
ago when he attended the A&E department.
Do not forget the heart as a possible focus of infection. The presence of
pyrexia, murmurs (especially if new or changing), microscopic haema-
turia, splenomegaly, the presence of central lines or features of heart failure
1hould lead you to exclude infective endocarditis. Was the heart prev1ously
normal? Look for embolic/immune phenomena of Roth spots (round reti-
nal haemorrhages with pale/white centres), Osler nodes (painful red sub-
cutaneous nodules at the finger tips) and Janeway .lesipns (blanchable red
macules on the thenar and hypothenar eminences), and infected emboli,
glomerulonephritis and splinter haemorrhages (IGS). Microscopic haema-
turia may be found. Splenomegaly is common. Clubbing is usually late.
ArthritiS of the large joints is common.
Remember the three main ways that congenital heart diseJlse can present in
the neonatal period. Remember- that ductal dependent lesions will only
become symptomatic when the duct doses, which can be any time from
day one until as long as the end of the first month. Remember that type 2
CHD lesions may re~mble sepsis and metabolic presentations and these
thould always be considered in your differential diagnosis. 25
R~member th.lt resp1r,1torv distre· ..; as a result ot cardiac lesions is mam
caused by pulmonarY ~..ongestwn and oedema secondary to heart failu lh
but also mily 1:-t.• the n.·~ult ot a dirL>et compressinn effect on the airwal '
{e.g. double a~rtic arch) or secondary to metabolic acidosis with respira~ 1\
ry compensation. .
11
- There are several cardiac causes that should be considered in a c:lriltf tvho co 1\
-~ Jnpses. These include cardiac arrhythmias caused by supraventricular tach) a
cardia, complete h~rt block, iong QT syndrome and the vasovagal attad
·~ Valvular disorders such as aortic stenosis should also be considered. It
::I three times more common in boys. It may p~nt with dyspnoea, chest pal
CJ) or syncope, especially with exercise. In the majority of cases the aortic \'ah
<( itself is narrow (\'ilh- ular) and often bicuspid instead of tricuspi1
Supravalvula:r aortic stenosis is associated with William syndrome ill1
E sub\"ah·ular aortic stenosis is assqciated with hypertrophic obstructive G\
co
>< diomyopathy or a fibrous diaphragm. Treatment is required if there is a pre
w sure gradient across the valve over 55-70 mmHg. As with all cardiac lesior
0
·.:::
.... antibiotic prophylaxis is required for dental and other types of surgery.
.S! - Beware of the dlild who is described as a mouth breather, who also snor(
"0
CD at night time and who develops cor pulmonale (right heart disease se
co ondary to respiratory disease) with possible dinical signs such as peripl
a..
eral oedema. The cause is cl1ronic hypoxiJJ leading to pulmonary hyperte;
sion, right ventricular hypertrophy ,and -eventually right-sided hea
failure. You may be shown cardiac catheter data of pulmonary hyper::te~
sion or ECGs with right ventricular hypertrophy and P pulmonale. Th
should be treated promptly otherwise the pui,Ihonary vasculac•. chang~
become irreversible.
- You should be familiar with the numerous syndromes that have cardil
lesions as part of their repertoire (see Chapter 14).
• Friedrt-ich ataxia - HOCM
• Marfan syndrome- aorti<. dissection, aneurysm and regurgitation
• Glycogen storage disease - type 2 cardiomyopathy
• Noonan sy:ndrome- pulmonary stenosis
• Roman<r-Ward !'yndrome- long QT interval
• Tuben,us sclerl">:ois - rhabdomyoma.
-You should also be a\•; are of some of the teratogens causing heart disea~
• Alcohol - ASD
• Rubella - PDA, coarctation of the aorta and tetralogy of Faltot
• Phenytoin - pulmonary stenosis
• Lithium - Ebstein anomaly
- PeriphertJI pulmo11ary artery stenosis, may be caused. by congenital rube!~
infection, Alagille syndrome and William syndrome.
- Remember that a baby with a stable cardiac defect such as a VSD may sud
denly become decompensated and go into heart failure with an intel'Clll
26 rent respiratory illness such as RSV ;,~fectiou. A s table cardiac def~t will
\e concurrent deYelopment of anaemia can produce a similar picture with
Ardiovascular compromise and heart failure.
nother clinical scenario that sometimes comes up is the term baby who
uddenly goes into heart failure in the first couple of weeks of life with a
al ECG, a normal or slightly enlarged cardiac shadow on the CXR and
0
AI
normal echocardiogram. There may be a wide pulse pressure on exami- a.
tion. The answer is an arteriovenous malformation {AVM) which may be a·
.nywhere, but listen especially over the liver, skull and kidneys for bruits. 0
Cyanosis may be present if a pulmonary AV malformation is present {right cc
'<
to left shunt). Rc:member however that the commonest cause of cardiovas- .
cular collapse and cyanosis in the first few hours with normal CXR a nd
ICC is transposition of the great arteries. ·
Another favourite trick q·uestion is the baby who is cyanosed centrally but
In whom all cardiac investigations are normal. Think of metllllemoglobi-
lllftmia (see Chapter 8).

Constrictive pericarditis can often give clinical signs that do not dearly fit a
classic .picture. Remember, however, that it mainly gives signs of right-
tided heart failure with ascites, peripheral oedema and hepatomegaly.
l'emember that all ,typesof pericarditis can give rise to constrictive peri-
r.ard.itis (except rheumatic fever). The question may give hints as to the
likely ae~ology: in an Asian family, for example, ~k of TB. ·
~t of heart failure in the first few months of life, together with ischaemic ..
dw\ges· on the ECG, may be caused by an anomalous left C(lr(Jnary artery: that
II, arising from the pulmonary artery. It usually presents after· a couple of
months when the pulmonary vascular resistance falls. Deep Q waves may be
Men on the EC.'G and the ·infant may <ieve\op mitral regurgitation. Treatment
Involves reimplantalion of the left coronary artery.
You may encounter questions where the child .has underlying cardiovas-
cular d isease and then develops acutely neurological.signs St!ch as a hemi-
FAresis. A couple of possibilities should be considered: they include either
lht' development of a cerebral abscess from an infected ~nibolus from a
rtght to left cardiac lesion or from an infected embolus on a valve. The
11ther possibility is a cerebral thrombosis secondary to polyeythaemia
caused by chronic hypoxia. Other causes of the coexistence of cardiovas-
' ular and neurological features include rheumatic fever, SLE, Lyme disease
and syphilis. ·
You should be aware of the features to look out for in a child suffering from
heart. transplant rejection. These include fever, prolongation of the PR
Interval on the ECG, reducing QRS voltages on the ECG and increasing
hNrt size on the CXR.
f'ulsus paradoxus describes when there is an exaggeration of the normal
drop in systolic blood pressure that occurs on inspiration (that is, > 10
mmHg). It may be caused by. tamponade, seven~ asthma, hypovolaemic
ahoc:k or tension pneumothorax. 27
Paroxysmal SVT
In a baby or child w ho is having ~ming episodes of pallor and sweatin
1
always think of paroxysmal SVf. Reme~"t:>er·''that sinus tachycardia rarer
exc~ds 180/min and SVT, is usually ove-c 210/m.in. There is arY extreme
regular narrow complex tachycardia on the ECG. Remember the causes I
SVT which include : 50% idiopathic and l:he remainder caused by CHD, f1
example· I:.bstein anomaly, Wolff-Parkinson-White syndrome, post..cardi1
surgery and sic~ sinus syndrome. Treatment involves ABC resuscitation fo
lowed by vagal manoeuvres (unilateral carotid massage, Valsalva .mar.oeuv1
in older children, eyeball pressure - beware the rare complication of retint
detachment, diving reflex- ice cold fuuulel applied to face of the baby), intrl
venous adenosine and if this fails call cardiologist and consider synchronol
DC shock. Recurrence of SVT is very common in·children. Other differentiJ
diagnoses of this presentation, tpgether With paroxysmal pallor and sweatinl
include phaeochromocytoma, recurrent hypoglycaemic attacks and benig
paroxysmal vertigo.

Tetralogy of Fallot
r
The previously pink child who is having cyanotic:: spells is a coxim;ton exam n
nation scenario. ibis may be the result of pulmonary infundibular spast
associated with tetralogy of Fallot. This occuxs most coiiUnOl1ly from a fe~ It
months until a couele of year-s of age, often precipitated by physical. activit, (\
The patient is usually distressed, anxioUs, cyanosed, often tachypnoel.c and, rt
old enough, may be squatting. This latter manoeuvre raises systemic bloo ...
pressure, reducing the t1ght to left ·shunting. Treatment ·involves oxyger I•
I knee-chest position, morphine and.intravenous beta-blocker administratior I

! Bicarbonate may be needed if there is a significant acidosis and - very rarel; 1


-emergency surg~ry.
Remember that the intensity of the murmur in tetralogy of Fallot l r
inve~ly proportional to the severity of the stenosis (that is, the more seven •
11

the stenosis the less the intensity of the murmur) because of the VSD presen
(the reverse to what one would· expect if there was no VSD). There is only 1
· single second heart sound in Fallot. The degree of cyanosis in Fallot is pro
pomona} to
the severity of the pulmonary stenosis and not the size of thl
VSD. The pulmonary stenosis protects against pulmonary hypertension.

Rheumatic fever
Although rare nowadays rheumatic fev~r still comes ·u p in the exam. The~
may or may not ·be a history of sore throat which may be foll9wed 2-4 weeks
later by the features described below. The first attack mainly occurs betwee"
5 and 15 years. Jones' major criteria are:
'
-Migratory polyartl•ritis (usually medium or larger joints} common.
-CArditis (common): There is a p;mcarditis and there will be clinical sigm
2~ related to whether my,ocarditis, endocarditis or pericarditis is presenl
(there may be a tachycardia greater than expected for the fe\·er, presence of
new murmurs - most often mitral - and aortic regurgitation, and
Carey-Coombs murmur: a mid--diastolic rumbling murmur at the apex
due to mitral valve oedema).
Sy dmhon(s chorea (occurring in about 10'~·;, of rheumatic case!>) may present
0

several weeks to months following the acute infecbon. Sydenham's chorea
rarely exists in the presence of card1ac involvement. Ch1ldren are describecl
a
0
as fidgety with sudden involuntary movemen$, often with altered.speech 0
cc
(and may demonstrate the 'milking sign').
'<
£r:ythemn mnrginntum: f'. non-pruritic maculopapular rash on the trunk and
limbs with a serpiginous border and central clearing.
Subcutaneous noaufes: Seen on the extensor surfaces of the knees, elbows,
wrist or even scalp and spine (usually nodules are seen after recurrent or
chronic rheumatic fever).
Minor criteria include .fever, arthralgia, previous rheumatic fever, raised acute
1•hase reactants (ESR, CRP), leucocytosis, prolonged PR interval (also look for
1AIIed Sf segments of pericarditis, inverted or flattened T waves of myocarditis
nr Var:ious degrees of heart block).
Tiie presence of two major or one major and two minor criteria is required
In addition to supporting evidence of preceding streptococcal infection
llncreas~d antistreptolysin antibodies (ASOT) titre, positive throat culture or
ttcent ·scarlet fever). The following differential diagnosis' should be consid- .
11rtd: systemic lupus erythematosus, juvenile chronic arthritis, Lyme disease,
ltfukaemia, gonococcal disease and Kawasaki disease, all of which have simi-
lArities in presentation. Treat with bed rest, high dose aspirin, steroids for
Arditis, and prophylaxis against recurrence (most common if there is persist-
lfts cardiac damage} with daily oral penicillin or monthly intramuscular peni-
IIUn. Chronic rheumatic fever (usually more than 10 years after the initial
111ck) causes valvular damage mainly affecting mitral and aortic valves.

tttrlcarditis
\child who presents with retrostemal chest pain that may radiate to the neck
nr left shoulder tip should have pericarditis excluded from the differential
•lltgnosis. The pain is central, sharp, poorly localising and varies with respi-
•a.tton., posture .and movement, and is often relieved by sitting forward.
It diaphragmatic involvement occurs then left shoulder pain may occur
htcause of innervation by the phrenic nerve (C3,4,5). On examination there
tnay be a scratchy sound heard best at the left sternal edge.
An effusion may develop causing a 'silent heart' CU\d the pericardia} rub to
U11ppear. If there is sufficient fluid build up, especially if it occurs rapidly,
lhtn tamponade may develop (the clinical condition is dictated by the rate of
• cumulation of fluid in the pericardium). Beck's triad: pulsus paradoxus
!Increase in the norrru.l physiological fall in pulse pressure on inspiration,
10 m mHg), increased jugular venous pressure (JVP) which increases on
lnaplration (Kussmaul sign) and decreased blood pressure. ECG changes 19
include saddle elevation (concave elevation) of the ST segme nts (except aVR)
with possible T wave inversion. A CXR may show a large globular hearl
shadow 'if there is an effusion. An echocardiogram will d emonstrate pericar·
dial fluid. Causes includt? infections, more likely if accompanied by fever and
associated source of infection such as pneumonia. In these cases a purulenl
pericarditis may occur. Viruses (about one-third of cases), for example
Cocksackie, ECHO. Bacteria (about one-third of cases), for example Haemophilus
-~ influenzae, Staph. mmms, Strep. pneumoniae, tuberculosis and fungal. Other
causes include JCA (especially systemic onset), SLE. rheumatic fever, malig·
·~ nancy including leukao>-{llic infiltration, uraemia, hypothyroidism_ post-car·
:::1
U> diotomy syndrome, trauma and irradiation.
<( Treat first by addressing the underlying cause. Administer NSAlDs for
.. pain. Drainage is necessary for tamponade. Antibiotics should be given for •
E
cu
purulent pericarditis.
><
w A CARDIOVASCULAR CLINICAL GUIDE .

-
u
·.:::
.!!!
"C
Q)
cu
Cardiovascular cases are extre:nely common short cases and long cases. It il
essential to have the examination of the cardiovascular system rehearsed t<
the extent that it becomes second nature to you. This makes you look confi
dent in front of the examiners and also enables you to concentrate on the diag
Q. nosis and creating a rapport with the patient. Here is an ordered system tha'
will take you smoothly through the examination and will also enable you !(
pick up any pathology on the way.
If given the choice to present as you examine or present at the end of youJ
examination, it is much better to present after you have finished your exami·
nation. First, you will have the opportunity to impress the examiner witl
your smooth uninterrupted examination technique. Second, it is much easier
presenting your case after having examined the whole system since you wil
have time to consider all your evidence in a systematic fashion. Third, an)
mistakes made early on in your presentation are more difficult to reverse and
only provide the examiner with ammunition to attack you later. Finally it i!
also much more difficult to perform two tasks well at the same time. Thif
applies to any examination system.
-Introduce yourself to the patient± mother.
- Ask permission and then remove the clothing from the ·upper part of th(
body (to the waist). Then place the child at an angle of 45•. (Alwaya
remember minor adjustments will have to be made for the smaller infant.!
- Observe the child from the end of the bed, particularly looking for dys
morphic features, cyanosis, respiratory distress, plethoric facies and obvl
ous scars from pre\'ious cardiac surgery.
-Take both hands and look at both aspects of each for dubbing, splintcl
haemorrhages, Osler nodes and tendon xanthomata. Examine the palmar
creases for pallor.
-Quickly feel both radials but then move swiftly to the brachial arteriet
30 They can be palpated better and the character of the pulse assessed mol\
ccurately, especially in the smaller. infant. Put one of your own thumbs on
ch of the patient's brachials (both pulses simultaneously). Assess for the
resence, rate, rhythm and character, and at the same time assess the res-
iratory rate. Lift the right arm upwards while still feeling the pulse for the
water hammer' pulse of aortic regurgitation. 0

Look at the conjunctivae for anaemia (only one eye needed}. a.

Ask the patient-to open his mouth and stick his tongue out to look for cen-
0
tral cyanosis. Get a quick look at the teeth and assess dental nygiene cc
(in other word~. the risk of b~cterial endocarditis). '<

Do not then start poking the child's neck for carotids since this will cause
distress. However, with prior explanation to the patient, place both index
and middle fingers of one hand on either side of the trachea in the
suprasternal notch to detennine if the ·trachea is in the midline. You may
also be able to feel a thrill of aortic stenosis.
Then feel for the position of the apex with the palmar aspects of your right
and left hands on each side of the chest wall (a similar manoeuvre to feeling
chest expansion in an older child, but with the fingers together pointing
towards the sides). With this method you should pick up a dextrocardia
with your left hand. Define the apical position accurately using the sternal
angle as a guide (second intercostal space); usually the fifth intercostal
apace in the mid-clavicular line.
Then with the ulnar border of the hand feel for thrills kt all the valvular .
areas (mitral - apex; aortic - second intercostal space right sternal border;
tricuspid - fourth intercostal space left sternal border; and pulmonary -
second intercostal space left sternal border).
Then with the ulnar border of the same hand feel over the apex for a left
ventricular heave and at the left sternal edge for a right ventricular
heave.
Place the bell of the stethoscope on the apex and listen (for low pitched
sound such as mitral stenosis- rare in paediatrics). Next listen with the
diaphragm (high pitched sounds). Listen in aU the valvular areas. Place a
finger on the pulse to time the heart sounds and any additional sounds, if
the patient is cooperative and not getting restless. Listen specifically for the
first heart sound (mitral and tricuspid closure) best h eard at the apex and
then the second heart sound (important in paediatrics and best heard in the
pulmonary area) and then for any !idditional sounds. For a murmur, be
su re to characterise it completely: site; radiation; timing (systolic/pansys-
tolic/continuous/diastolic); intensity (grade 1 to 6 for systolic and 1 to 4
{CJr diastolic}; and character (e.g. harsh, rumbling or blowing). If a systolic
murmur is heard then you should also listen over the carotids, apex and
the rest of the precordium for radiation. (See later in this chapter for a
method of diagnosing cardiac murmurs.)
Use the time when auscultating to put all the clinical signs you have elicit-
ed so far together. 31
-Tilt the patient forward and listen over the back for the radiation of mur-
murs. Ask the patient to breathe deeply with the mouth open to listen for
inspiratory crackles (especially at the bases). When the child is leaning for-
ward take this opportunity to look all around for scars and don't forget to
lift up both arms completely since thoracotomy scars may be hiding. This A
can be done earlier in the examination during initial inspection if it is easier

-~ for you to remember it at·this point. Minor adjustments to the examination


-will be required for the smaller infant.

·~ - Palpate the abdomen for hepatomegaly.


:::J
Cl) - T~t for pitting oedema ovenhe shins.
~
.. - Then tell the examiner that ideally you would like to:
E 1. Measure the blood pressure (and radiofemoral delay and four limb
n:s
)( blood pressures if appropriate).
w 2. Plot the height and weight on growth charts.

-(,)
·.:::
.~
"C
C1)
n:s
~senting to the examiner
- .Do not look at the patient, look ?!t the examiner.
CL.
- Remember that the examiner has been watching you examine the patient
and does not want a detailed account of this. In all presentations of clinical
findings after an examination I think that there are certain vital points of
information that need to be presertted followed :by any relevant positive
clinical findings. Thus continue: ·
PI
- ' I would like to present my.fintlings on the cardiovascular examination of bi
{for example} Emilie'·(always a good idea to remember the child's name).
-General ob~ervations. Always mention the ;presence .or absence of Ill
cyanosis, respiratory distress at rest and dysmorphic features. Mention the
following if present: scars, clubbing, pallor. t
II
-Then mention the pulse (rate, rhythm, character), apex beat position (dis· ~
placed/not displaced), heaves or thrills, first and second heart sounds l
(normal/abnormal). Since the second heart sound is so important in the
paediatric examination one can mention that there was normal/abnormal
splitting of the second heart sound. Then go on to describe the murmur as
described above.
-Mention the'presence or absence of signs of heart failure, in particular the
liver and oedema.
- Most of your marks will now have been awarded if you have carried this
out competently. But now comes the time where you have to put your clin·
ical findings together. Simply say that these findings are consistent witll
(for example) a ventricular septal defect
- If you cannot put your clinical findings together do not make one up bul
32 : say that you are unable to formulate a diagnosis.
.....--1-- ..
!

: 'J
I
1
( 1)
2)
Pulmonary flow murmur
Pulmonary stenosis 0

Aortic stenosis
1 3) Atrial septal defect ....
I ''., 4) Patent ductus arteriosus 9:
0
0

:
------ I ----....._
.· cc
__ _ __ )
_ Ejection '<

I
... .,._ _. systolic

--- --·- - I
Pansystohc
Tricuspid ( I
regurgitation : I
1) Ventricular septal defect
/ I
I
2) Mitral regurgitation
3) Stills murmur
I
I \
I '
''
I
I '

!
Rg. 2.3 A scheme for diagnosing the nature of heart murmur lesions in paediatric.s,
based on where the murmur is heard loudest.

llotes on the CVS examination


There is a useful rule for determining the likely lesions responsible for systolic
lllurmurs in children: divide the chest into four quadrants with a vertical line
lhrough mid-sternum and a horizontal line through the level of the nipples
tee Fig. 2.3).
Having examined the patient, determine in which of these four quadrants
die murmur was heard loudest. This is usually obvious in children.
The pansystolic murmurs are usually heard below the level of the·nipples
lnd the ejection systolic murmurs are heard above the level of the nipples. Thus
If a m urmur is heard louder above the level of the nipples then it is ejection sys-
!f>lic and if the murmur is heard louder below the levd of the nipples then it is
pansystolic. This is very useful to know since the distinction is not always clear
In children and infants who generally have faster heart rates (see Fig. 2.3).
-Lift upptr quadrant: pulmonary flow murmur, p ulmonary stenosis, atrial
septal defect and patent ductus arteriosus (the last gives an ejection systolic
murmur in younger infants and a continuous machinery munnur with
systolic accentuation in older children). 33
- Rigllf upper qun,frant: aortic stenosis.
- Rigllt lc>u'l!r quadrant : tricuspid regurgitation (rare).
- L~ff ltmw quadrn11t: \'entricular septal defect, mitral regurgitation, Still's
murmur (see later).
Flow murmurs are more likely in high cardiac output states such as anaemia,
thyrotoxicosis, following exercise and with fever. They are best heard in tht?
pulmonary area. Atrial septal defect causes a pulmonary ejection sy~t~lic
murmur as wetA as a mid-diastolic murmur (if there is a 4rge shunt) as well
as fixed splitting. of the second heart sound.
Continuous murmurs are the result of a combination of a systolic and a
diastolic murmur, caused by connections between the aorta and pulmonary
artery such as occurs in a patent ductus arteriosus, arteriovenous anasto·
moses or over collateral vessels over the back in, for instance, coarctation ol
the aorta.
A third heart sound is normal in children and is caused by early diastolic
filling following the aortic component of the second heart sound

Functional murmurs
These are asymptomatic, systolic (never diastolic), short, not loud (< 3/6),
heard over a limited area of the precordium, with a normally split second
heart sound, changing with posture, not associated with heaves or thrills with
normal investigations such as ECG. CXR and echo.
- Venous hum (the result of blood coursing through the systemic large veins
in the neck) is a blowing continuous murmur heard just below the
clavicles. It varies with changes in position of the neck and respiration.
-=-Pulmonary flow nwmltlr is a soft ~ection systolic murmur in the
pulmonary area.
-Vibratory mumwr (Still's murmur} is a short buzzing murmur heard over
the left lower sternal edge or apex which changes with posture and usually
disappears by puberty.
If there is a murmur that is post surgical correction (that is, scars are present),
then the murmur is usually the result of pulmonary or ~ortic stenosis (this
does not obviously relate to the more complicated correcte<L9rdiac lesion).

Thoracic scars
The other rule that is useful to know is which likely operativ~ procedure was
responsible for what thoracic scar.

Right thoracotomy scar


- Blalock-Taussig shunt
- PDA ligation.

Left thoracotomy scar


- Blalock-Taussig shunt (feel for absent pulses in the ipsilateral arm)
- PDA ligation
Coarctation of the aorta repair
Pulmonary artery band ing (listen for a murmur)
Lung biopsy (look for other evidence of lung d isease).

Mld•stemotomy scar
Any major bypass surgery. for example valvular repair or one of the more
complicated cardiac repairs.

J
Th• second heart sound
1 A 1pecial mention should be made of the second heart sound since it plays an
1 Important role in the paediatric cardiovascular examination. Under normal
· t lrcurnstances the aortic valve closes before the pulmonary valve: this is
u lled physiological splitting of the second heart sound and increases on
lnapiration. Wide splitting may be caused by right bundle branch block and
pulmonary stenosis. Fixed wide spliW.ng may be caused by an atrial septal
tlefect. Reversed splitting (pulmonary component heard before aortic compo-
lltrnt) may be caused by left bundle branch block, severe aortic stenosis and
lwft ventricular failure. Narrow splitting of the second heart sound may be
t:aused by pulmonazy hypertension and aortic stenosis. A loud pulmonary
component of the second heart sound is heard in ·pulmonary hypertension
•nd a loud aortic component in systemic hypertension.
A single second heart sound may be caused '?Y tetralogy of Fallot, pul-
monary atresia, single ventricle, aortic atresia and pulmonary atresia.

/
35
Respiratory
system 3
You should be familiar with th~ definitions of lung volumes and capacities.
You should also know about tl\e spirometer ttacings demonstrating the dif-
fttent lung volumes and capacities. This may well present itself in the form of
A data interpretation question or in the viva.

OBSTRUCTIVE AND t.RESTitlCTIVE' LUNG DtSE:ASE , · ~··· ·


You may encounter lung volumes in the data interpretation questions. Be
lamiliar with th~ changes that are expected in:
Obstructive lung diseases (such as asthma, bronchiectasis, emphysema or
cystic fibrOsis).
Restrictive lung diseases (interstitial lung disease such as fibrosing
alveoli tis, neuromuscular disorders such as Duchenne muscular
dystrophy and musculoskeletal disorders such as severe kyphoscoliosis).

Obstructive
Air trapping is the main featu~e.

Increased: residual volume, functional residual capacity and total lung


capacity.
Decreased: vital capacity.

._trictlve
Utually smaller lungs which are unable to expand fully.
Decr.eosed: vital capacity, functional residual capacity, residual volume, total
lung capacity, expiratory ~rve volume.

lllOOO;GAS;INTERPRETAt'UlN ... . .: : · ,., ,. . :


fhe&e are common questions with which you should be at ease. These ques-
llnns may be in the guise of It neonate on a ventilator, or taken from a child ·37
'" order to increase the P01 and increase the PC01 simultaneously try
Here we will d~t'SS 'the que ti
with some respiratorv disturbance .
';e.tabohc disturbance or other proble
s ons at relate to respiratory problems. Increasing the PEEP.
Another manoeuvre in order to increase the PC0 2 is to extubate the baby
(In a baby whose ventilatory function is adequate and possibly fighting the
The neonate on the ventilator ventilator), or if ventilation is still necessary one can increase the dead
You should be familiar with these . . . apace by mcreasing the length of the ET tube.
of the general principles. from chmcal practice but this is a summa

-First look at the pH to detennine •'f there IS


. an actdosiS
. . or alkalosis am
Thepies
scenario ~:.ere a previously stabl~ premature neonate on a ventilator
-Then determine if thisf has a res~tratory
. . tuddenly ' collapses' with the following blood gas picture·
looking at the PCO or a metabolic cause. This is done b
' or a resptratory cause ( aised .
and reduced in respiratory alkaJ . r m respiratory acidos· pH 7.03
bonate for a metabolic cause (I os~) and the base excess/deficit and bica PC02 11.4
metabolic alkalosis) Th ow m a metabolic acidosis and raised in P01 5.9
P e, an acidosis caused by a r~ .
1 . ere mav of course be a mixed .
ptcture with, for exa HC03 23.7
sated for by a metabolic ch rra~o:r or metabolic cause being compe BE -3.5
piratory change (retaining ange retaliUJlg or excreting hydrogen ions) or I here is a severe respiratory acidosis of sudden onset. There are several pos-
.. . or excreting CO ) resn~>cti I R
resptratory compensatory effect in res 2 r - ve y.. emember that tll
not be possible in the case of a . . ponse to a metabolic disturbance ma lllble causes: these include:
r
~'-- . · . neonate who is on a , til
t uiC' premature kidn . . lso u. . . 'en ator.
Als.o remem - Dislodgement of the endotracheal tube (listen to the lungs and look for
A tha
_ be C'f.lS.a less emoent at adci--l,)~homeostas·
chest movement).
premature baby who has RDS is uall . · - Blocked tube (listen to the lungs and look for chest wall movement).
tial settings that vary between ~ b Yventilated with the Iollowing ini
ranges: uru ut are usually within the followi.n -Ventilator or generator failure (inspect the ventilator).
- P~umothorax (transilluminate chest :t X-ray).
- Intraventricular haemorrhage (exclude with cranial ultrasound).
Rate 60-80/min
Fi02 0.7-o.s 2. A 32-week gestation baby is bom with tachypnoea, grunting and inter-
PIP 18-28cm H,O costal recession with the following blood gas at a few hours of life.
PEEP 3-5 em I:izo-
Inspiratory time 0.3-{)5 s 7.03
9.8
F~r pulmonary interstitial em h sema an . 7 5 (in 68~o Ol)
ston comparatively high p y . d persiStent pulmonary hyperten
er rates wtth shorter · . 13
t ower peak inspiratory p mspuatory times are used
tha I . . ressures can be utilised -11.1
When constdermg questions th t . .
a baby with abnormal blood a requsre you to alter ventilator settings . This shows a mixed respiratory and metabolic acidosis. This is most likely
to be a result of the respiratory distreSS syndro~- In order to correct the
. gases the following need to be remembered
1. In order to mcrease the PO the 55. . . . · . · acidosis the Tespiratory and metabolic problems should be attacked simul-
- Increase the FiO Th' 2 po tbtlities are: tanrously. The metabolic acidosiS can be treated with volume expansion if
1 2· 1s would be your fi
already high and approachin 0.7. rst step unless the FiOl is
clinically the baby has reduced perfusion, or bicarbonate if the baby's per-
The next .step m·•g ht b e to mcrease
(PIP). . g the peak inspiratory pressure fusion appears adequate. Alternatively 11iAM can be used (advantages of
this drug include no sodium load and lowering of C01 but it may cause
- Th
Increase the inspiratory ti me. respiratory depression). The b3by will require so~ form of ventilation in
- en consider increasing the eak
~~embering that high PEEP~ red~d expiratory pressure (PEEP)
. order to control the hypercapnia and oxygen requitements.
inhib tt cardiovascular funeti' P pose to pnoumothoraces and can 3. A 4-year-old child presents with a history of chronic middle ear effusions,
on.
snoring and failure to thrive. The arterial blood gas when asleep shows:
2. In order to decrease the PcO
- The most important ma :!. the following are po&JSbllltil$
noeu\'re ·s t · pH 7.40 39
- Increasing the PIP ·u lso ' o tnCf't'I\!>C the mt•.
38
WI a decrease the flCQ., .. PCOl 9.1
PO. 7.8
HC03 33
This child has a compensated respiratory acidosis. There is compensation
since the pH is normal (and bicarbonate is high} despite the markedly
raised PC02• The clinical history gives us a due as to the possible aetiolo
gy which in his case was enlarged adenoids and may be part of th~
->ns obstructive sleep apnoea syndrome. The child should have a formal sleep
study performed looking at the oxygen saturation trace and episodes ol
·~ obstructive apnoea. Remember the other possibl~ causes of hypercapnia il1
::s a child, which may be a result of central respiratory depression (e.g. cen·
C/) tral depressant drug ingestion}, respiratory neuromuscular disease (as in
..
<( Guillain-Barre syndrome} and thoracic wall disorders (e.g. severe scolio- 1
sis) and obesity. 1
E
~
4. The hyperventilation syndrome should always be considered in a child
who presents with a respiratory alkalosis with no abnormal clinical.or lab·

-0
·c
.!!!
'C
Q)
ns
oratory findings, especially if the P02 is normal. Such children are typically
anxious individuals. Respiratory stimulant ingestion and the early stages
of salicylate overdose should also be considered.
5. A baby bom at term who is one week old is brought in to the casualty
a.. department grunting and periph~aUy shut down with a respiratory rate
o£80/min.
7.08
1.9
75
11
-18.8
This is caused by a severe metabolic acidosis for which the baby is attempt·
ing to compensate by hyperventilating and thus blowing off COr
However, the pH shows that compensation is incomplete. The most likely
cause of this picture in this baby would be group B streptococcal sepsis,
congenital heart disease or a metabolic disorder.

Respiratory failur·~ is defined as a PaOl of less than 8 k.Pa. It is divided into


two tyt>es based upon the PaC02.
-In type I respiratory failure there is a low PaC02 , usually less than.
6.5 kPa. This is the result of a pure ventilation-perfusion mismatch
causing a failure of gaseous exchange. The consequent
hyperventilation causes the blowing off of C02 (which. cannot oc;:cur in
the case of oxygen because of the nature of its disassociation curve).
Conditions causing this type of failure are: pulmonary-embolus,
pulmonary fibrosis, pulmonary oedema and asthma (hypercapnia in
an asthmatic patient with a severe attack is a sign that suggests the
40 child is tiring or becoming severely obstructed).
In type 11 respiratory failure there is pure hypoventilation causing a low
l'n02 and a high PaC02, usually more than 6.5 kPa. This can be caused by
Jf central respiratory depression, neuromuscular disorders, thoracic wall
11 disorders and pneumonia.
0

~ expiratory flow measurements (PEFR)


d'••k
~ I htse can be measured properly only from about 5 years of age. They are
n u~eful for assessing the severity of asthma attacks and the response of the
iJI1••1lent to therapy. Normal values are available and relate to height. An
o Improvement o f 20% or more following inhaled bronchodilators is diagnos-
llt of asthma. Remember morning dips in PEFR as a sign of possible wors-
ld nlng of asthma.
f>.
IJ' lplrometry
~
11\Js can provide a spirogram (expiratory volume as a function of time, an
••piratory flow-volume curve and a flow-volume loop comprising inspira-
.y tlon and expiration).
Forced vital capacity (FVC). This is the total amount of air exhaled during
maximal expiration. FEVl is the forced expiratory volume in the first second.
The FEVl /FVC ratio is useful in determining whether there is a restrictive or
obstructive component. Normal values of FEVl and FyC are available for
age, height and sex. Be familiar with spirometric graphs of volume against
time and their interpretation. ·

Restrictive pattern
Here -the ·FVC .is -reduced but so .is :the FEVl 'resulting in a normal or occa-
•lonally ·higher F.EVl /WC (e.g. 90%, usually about 75-80%).
This is caused by neuromuscular disorders, skeletal thoracic cage defects
Including scoliosis and interstitial lung disease (resulting hom, for instance, sar-
~oidos.is, extrinsic allergic alveolitis, pnewnoconiosis, fibrosing alveolitis, post-
n~diation a..<d drugs). All of the interstitial lung diseases are rare in childhood.

Obstructive pattern
Here the FEVl is considerably reduced compared to the FVC resulting in a
low FEVl/FVC (e.g. 40%).

Flow-volume loops
The diagrams ·in Fig. 3.1 rorrespond to maximal flow rates measured at vary-
Ing lung volumes. These loops· are useful in investigating the site of possible
obstruction in the respiratory tree. Proximal obstruction of the upper airway
(e.g. at the level of the trachea) reduces the flow rate at high lung volumes,
I.e. at the beginning of expiration, whereas obstruction lower down the air-
way (e.g. asthma) reduces the flow rate after further expiration when the lung
volume is low.
~1
a) Normar lungs b) Obstructive lung disease

FEV1.1..1.
Expiratory Expiratory FVC!
flow I ;..f-"-'~'--''r" flow
FEV1/FVC
Vsecond Vsecond
RV

-.:::
tO
Inspiratory
flow
Vsecond

'::J=
CJ)
c) Restric1ive lung disease d)
..
<(
FEV1! ,
... - ... '
E Expiratory FVC,J. Expiratory

~ flow
FEV1/FVC normal
flow
Vsecond
w Vsecond 1

-0
·.::
-~
"0
Cl>
tO
RV
Volume(I)

fn.~ratory
flow
Vsecond

Q.
e) F"axed airways obslruction ----Clbs1ructlon
Variabl9 extrathorac\c

Variable inttathoracic
---obstruction
Expiratory
flow
Vsecond
RV
Volume (I)

fig. 3.1 Typical spirometric findings seen in normal children and in children with
various pathological states.

Arterial blood gases


These have been described earlier.

Transfer factor {Tl.CO)


This is a useful meaSttre of the transfer of a gas across the alveolarI capillary
interface. Basically, it involves determining the amount of carbon monoxide
absorbed across the alveolarI capillary membrane following an inhaled held
breath of carbon monoxide. It is dependent on a number of facto: s which
include: {a) alveolar ventilation; {b) blood flow to lungs; (c) haemoglobin
concentration; (d) lung volume/surface area; (e) age: its value increases
42 throughout childhood.
- Decreased TLCO: parenchymal lung disease (inflammation, inflltration,
fibrosis), reduced pulmonary blood flow (pulmonary embolus,
pulmonary hypertension, emphysema), \'entilation/perfusion mismatch
(e.g. pneumonia, pulmonary oedema), anaemia.
- Increased TLCO: polycythaemia, exercise (higher in athletes), pulmonary
haemorrhage, for example pulmonary haemosiderosis (raised initially
following bleeding but with time later falls due to fibrosis). TLCO is
usually normal but may be increased in asthma.

Pleural effusion aspirates


The effusion can usually be classified into a transudate or exudate depending
upon the protein content of the fluid. Protein content < 30 g/l implies a trans-
udate and·> 30 g/1 implies ~n exudate.
- Transudates are usually bilateral and are caused by filtration of fluid
_ through capillaries into the pleural space. This may be caused by right-sided
heart failure, fluid overload or any condition causing hypoproteinaemia
(e.g. nephrotic syndrome, liver disease and protein-losing enteropathy) and
also occasionally ~een in hypothyroidism.
- ~dates are ca~sed by inflammatory processes such as infection or neo-
plasia. Causes include pneumonias including tuberculosis, lympho~as and
tOnnecQ.ve tissue di,seases. Jn addition to finding a protein count in excess of
30 g/1, other investigations are important in narrowing ,down the diagnosis
and Some of these are listed: here: (a) microscopy, culture and sensitivities
(MC&S) for microorganisms; (b) Ziehl-Neelsen stain for add fast bacilli; (c)
l'Ytology for malignant cells; (d) differential white cell count: lymphocytosis
Ia associated with leukaemic infiltration, viral infection, TB. Neutrophilia is
41S0ciated with a purulent bacterial illness. Eosinophilia is associated with
parasitic infections (which often spread to the lungs as part of their life cycle).
Remember the possibility of the effusion being a chylothorax or haemothorax.
A haemothorax mainly occurs following trauma or surgery and is immedi-
Ately obvious from a bloody pleural aspiration.
A chylothorax contains triglycerides which give it a milky colour (though
not if the patient has not eaten for some period of time). It is caused by dam-
•ge to the thoracic duct at the root of the neck usually secondary to trauma
(lnduding traumatic delivery in the newborn), surgery (most often cardiac
aurgery) and neoplastic .disease. A purulent effusion may look the same, but
If the sample is centrifuged then the white cells can usually be cleared from
the liquid but this is not the case with a chylothorax which remains milky.
Treatment consists of continual drainage of the chylous effusion (beware of
NSultant fat-soluble '\·itamin deficiencies as well as electrolyte and lympho-
cyte deficiencies if the effusion is large and drainage is prolonged). Medium
chain trlglycerides are given as the main source of fat as they bypass the lym-
phatic absorption and are transported directly into the portal vein. The effu-
lllon usually settles after a few days or weeks but if it persists surgery may
become necessary. 43
_
Table 3.1 Summary
_ _ _o1
Organ affected
_the
__ clinical
:.._ manifestations
_ - - - - - -of __
. :cystic.
Clinical manifestations
. fibrosis .~

Respiratory tract May present early with a raised respiratory rate,


hyperexpansion of the chest, inter....,stal recessior and
cough. Later, recurrent chest infections occur (thE
commonest presentation) with the usual paediatric
respiratory pathogens and later with Haemophi/u
influenzae, Staph. aureus and Pseudomonas aer.u7inosa
(more rarely with Klebsiella. Proteus. Se"atia and
Pseudomonas cepada - this occurs in the more
debilitated older patient and may cause a rapid decline
in respiratory function). Bronchiectasis develops lhith
patchy areas of collapse and consolidation. Haem:>ptysis,
pneumothorax, cor pulmonale and respiratory faHure
develop later. CF is ~sociated with allergic
bronchopulmonary aspergillosis.
Gastrointestinal tract One of the earliest manifestations is meconium ileus
(occurring in about 15% of cases) which can pr.~ <.,nt with
obstruction, volvulus, perforation and distal g:..< atresia.
Panc:reatic insufficiency may also be an early manifestation
in the form of steatorrhoea and bulky, pale. smelly stools
in a greasy film which are difficult to flush away.
Malabsorption causes failure to thrive and deficiency of
the fat-solub~ vitamins A. D, E and K (second commonest
presentation). Failure to thrive occurs despite a very big
appetite. Pa11creatitis secondary to duct obstruction may
occur. lOOM occurs in about 10% of cases. Bile duct
obstruction leads to a secondary biliary cirrhosis in some
patients with accompanying portal hypertension (with
splenomegaly, "hypersplenism and oesophageal varices).
Gallstones o~cur in about 10%. Rectal prolapse occurs in
up to 20% of children. Meconium ileus equivalent (distal
intestinal obstruction) can occur in older children with less
acute symptoms d. m.e conium ileus and presents with
intermittent colic.. constipation and possibly vomiting
caused by repeated partial bowel obstruction as a r.esult
of the viscous mucus production. A palpable mass in the
lower right quadrant is sometimes found. Gastrograffln. a
high osmolar contrast liquid. may dislodge the,ptug.
ENT Sinusitis is common and occurs in the majority. Nasal
polyps (associated with less severe chest problems)' may
occur in about 10-20% of cases.
Reproductive system Delayed puberty (as with all chronic illness in
children). Reduced female fertility because of
abnormal cervical mucus production, Males are almost
always infertile as a result of atresia of the vas
deferens and epididymis.
Skeletal Short stature {as with any chronic iUness in childrem).
Hypertrophic pulmonary osteoarthrop~hy {inciudimg
dubbing).

44
• Table 3.1 Continw'ed
Organ afle<ted
-"--·--------
- -- ·---- ---1
Clinical manifestations
-··--· - of ~~at c.ontah"1ing excess
·- - - B~use ~-·--- ·---------
quantities of salt.
:sweating- ~any in hot weather- may cause heat
strolt~ .00 tardiOYaSculiJr cotra~. Right-sided heart
iallure may develop secendary to \'U!monary
llypertP.mion.
Metabolk Remember that in infzmts 0: is one .of the .:.a~ of a
hY?Mat~aemic hypochtor.<:Jemk :-:~Aetabolic 3llmh;,sis
(know 1M othen in the list).
H•ematologlcal -------~----------
Anaemia of thronic disease, usually ncrmorftk
normochromic 4naemia. Remember that the ~rritin may
be raised as it is an acute phase t;eactant.

CYSTIC FIBR.OSIS (CF) .


AI the commonest inherited disease in the Westem w orld, cystic ~brosis
comes u p routinely in the written and clinical parts of the examination:
,_.m-relevant aspects a re covered below (see Table 3.1). The ge netics chap-
ter (Chapter 1) discusses the genetics of cystic fibrosis, w hich causes a dys-
function of the exocrine glands resulting. in viscous secretions affecting
many organs.

Investigat io ns
Antenatal diagnosis: This ~y be per formed ,by chorionic villus sampling
(8-10 w eeks) o r am:niocentesis at 16-18 weeks with ONA ana lysis.
Sweat test: Piloc-arpine iontophoresis induces sweating (usuaHy on a small
area of skin on the foreann) and a sample of more than 100 mg is
collected. ~sodium concentration of more than 60 mmol/l is required on
more than one sweat test to confirm the diagnosis. Values between 40
and 60 mmol!l should be repeated.
DNA analysis can be performed in order to identify the most co mmon CF
mutations (see Chapter 1).
Newborn screening: Serum immunoreactive trypsin is markedly raised in
newbom babies with CF. Accuracy of the test is improved with the use of
monoclonal an tibodies. Confumation with other tests as above.

C.uae.s of a false positive :Jw eat test


• Adrenal insufficiency
• Congenital adrenal hyperplasia
Diabetes insipid us
• Glucose-6-phosphatase deficiency (G6PD)
• Ectodermal dysplasia
• HypothyroidiSm
• .Mucopolysaccharidoses.

45
There are a wide range of possible X-rays that you may encounter in the slide
section of the written examination as well as in the clinical exam.
Q) Radiological examination of the respiratory system may involve a pl<!iu
:E CXR, barium swallow, ultrasound, cr and·MRI. Usually some sort of brief
::s history is given with the slide.
(!)

.~ Chest X-ray
~ A ~ method for looking at a CXR is the fo~lowing.
::s
U)
<( 1. Look at the name, date of birth and, date of the examination.
.. 2. Make sure that the orientation of the radiograph is correct (Land R). If the
E
C'CS right mark is on the same side as the cardiac apex then think of dextrocar·
)(
dia (if the X-ray has been labelled correctly).
w
(.) 3. Determine whether the film is PA (posteroanterior) or AP (anteroposterior).
:s PA is the routine film: an AP film will usually be labelled as such.
-~ Other.vise an AP film can be recognised firstly :because tlte scapulae over·
"0
Q) He the 1\mg fields (this is not the case in a good quality PA .film) and sec-
C'CS
0. ondly- the chin is usually seen on an AP. No comment can be made of the
size of the heart in an A!? view fihn and the cardiac silhouette appears latger
than in ·a -PA. AP views are usually obtained in the sicker patient who can·
not stand.
4. Comment ..on the penetration l.)f ~;film. In an over-penetrated film the
1\ulg .fields appear very dark with few v.ascular markings. One should
ideally just be able to make. out the vertebrae behind the <:ardiac
shadow.
5. Orientation: make sure that the patient is not rdtated by looking a t the dis·
tance between the spinous processes and the med2a1 ends cl abe ~des
which should be equal·on both sides.
6. InfL'ltion: this is important in paediatrics since hyperinflation is a common
finding. A normal CXR in inspiration will show the diaphragmatic level a1
rib 8-9 posteriorly and ~b 6 anteriorly. Flattening of the diaphragm is also
an important finding in hyperinflation. In 90% of children the right. dome
of the diaphragm is ,higher than the left.
7. Now you are able to go through the CXR systematically: heart, medi
astinum (trace the out~~ne of the mediastinum visually),lung fields, vasetl•
lar markings (a sense of what is normal comes with experience but roughly
speaking pulmonary vessels should no~ extend beyond two-thirds of ttw
width of the lung fields), diaphragm, bones, soft tissue ari.d you may ~
able to see some abdominal pathology on a CXR (such as air under tht
diaphragm in the case of a perforated bowel). The right heart border supe
riorly consists of the SVC and inferiorly the right ventricle. lhe'left heart
border consists of (from top to bottom): aortic knuckle, left pulmonary
416 trunk. left atrium and theu left ventricle. ·
~. Comment on the need for a lateral film which may help localise a lesion to
a particular lobe or segment of the lung or pick up pathology that might be
mi:;~d on a PA film (especially in the anterior mediastinum).

Always remember that an enlarged superior mediastinum in an infant less


than a few months of age may be due to the thymic shadow. There is usually
• characteristic sail sign. The cardiothorackra·t io in a PA film is usually 0.5 but
tnay be slightly higher in a child under 2 years of age. Remember that the
heart diameter may vary by up to 1 em during the cardiac cycle.
- Look for evidence of shifting of the lung or mediastinum (e.g. following
lung collapse) by looking for movement of the hilum, trachea or fissures
from their expected·positions.
- Any increased density should be described as an area of increased slli7d-
Otving. Linear shadows are described as Teticular, dot-like shadows are
caJled nodular and fluffy diffuse shadows are known as alveolar shad-
owing. Remember that loss of clarity of the right border of the medi-
astinum corresponds to right middle lobe pathology. Loss of clarity of the
left border of the mediastinum corresponds to pathology in the lingula.
The area above the right hemidiaphragm corresponds to the right lower
lobe.
A pulmonary sequestration, most common in the left lower lobe, is where a
lobe of the lung receives a blood supply distinct from the pulmonary artery
and m 'fact a~ from the systemic aortic blood supply. It has a venous
drainage into a pulmonary vein. Their presence is_associated with an
Increased risk of chest infections which are often recurrent.
The scimitar syndrome describes the case of a hypoplastic right lung (espe-
cially right upper lobe) which has a systemic arterial blood supply and a
venous drainage into the subdiaphragmatic vena cava and is often associ-
ated \1\ith the presence of an ASD. A CXR reveals a crescent-shaped shadow
next to the right heart border.
Cystic ade~tomatous. malformations are caused by irregular dilatations of the
bronchi leading to variably sized air-filled cysts that are usually found in a
lingle 1~. If widespread it may present at birth with respiratory distress
and may require surgical resection.
U they are large, couge~tital lung cysts may cause a compensatory collapse of
adjacent or contralateral lung tissue. Remove because of the risk of infec·
tlon and possible malignant transformation.
Congmit11llobar emplrysema mainly affects the right or left upper lobes (and
less commonly the right middle lobes). It is caused by a weakness in the
wall of a lobar bronchus resulting in hyperinflation of the affected lobe or
lobes (caused by a .ball valve effect). The emphysema may cause respiratory
distress in the neonatal period (wheeze, tachypnoea and poor feeding)
with all the features of a unilateral hyperinflation (such as hyperresonance
and reduced breath sounds). The·CXR shows radiolucency in the region of
the affected lobe together with possible compression effects such as the -·47
co
collapse of adjacent lobes or mediastinal shift. Treatment of symptomatic ~
individuals involves resection of the affected lobe. "1
- Rl!spiratory distress syndrome is a common slide. Look for hypoinflated, tt:
dense lung fields with possible atelectasis, ground glass appearance of the /,
lung fields and the presence of an air bronchogram (caused by the air-filled if
airways surrounded by dense lung tissue). Also look for the endotracheal l
->
C'O
tube (if ventilated) and other common neonatal devices such as a chest ~
drain, UAC or UVC. Diffenmtial diagnosis of RDS is total anomalous pul· <
·~ monary venous drainage (fAPVD) or bilateral pneumonia (most com· l·
::;, monty group B streptococcal pneumonia). 1
rn
<t - Meconilml aspiration syndroi11e causes hyperinflated lung fields with flat·
tened depressed diaphragms and patchy areas of consolidation leading to
E radio-opaque lung fields as a pneumonitis develops.
C'O
Transient tachypnoea of the newborn (lTN).shows streaky lung fields (espe- ~
><
w -
0 cially perihilar) and fluid in the fiSSures. ~
...
·;::::
.!'2
-Bronchopulmonary dysplas~ shows hyperinflated lung fields interspersed :
"C with areas of atelectasis, cystic changes, bronchial wall thickening and dif·
CP fuse reticular shadowing.
C'O
0.
-Pulmonary hypoplasia is caused mainly by: (a) oligohydramnios; (b) lung
compression in utero, for example diaphragmatic hernia; (c) reduced
breathing activity in utero, such as Werdnig-Hoffmann disease. CXll
shows dense hypoinflated lung fields which often have a bell-shaped
appearance. Confirm with lung function tests.
- Tracheo-oesopluzgeal fistula is usually diagnosed by failure to pass a size 10
catheter into the stomach because it has become coiled up in the atreti(
oesophageal pouch. X-rays will confirm this as well as noting the presenct
of air in the stomach which can occasionally be followed to the level of tht
tracheo-oesophageal fistula. The presence of air in the stomach confi.rml
the presence of a fistula between the distal oesophagus and the tra~ea.
-Cystic fibrosis may come up in a rad iology question in several ways. A plai~
abdominal X-ray of meconium ileus will usually show dilated proximnl
loops of small bowel with a ground glass appearance in the region of th(
caecum (a barium enema may show a distal microcolon}. A CXR show1
hyperinflated lung fields with patchy atelectasis. There is peribronchial
thickening and aree~s of bronchiectasis (thickened tram.-line shadows). Yo11
may be shown a bronchogram demonstrating bronchiectatic airways.
-Asthmatics present with hyperinflated radiolucent lung fields caused by air
trapping (presenting as an increased number of ribs counted in an inspirn•
tory film witl.\ flattened diaphragms). Look also for pneumothorax, pne11
momediastinum. infection and an inhaled foreign body that may help
explain the clinical p:esentation.
- A pneumothorax is seen on an X-ray (best on an expiratory film) as a radl
48 olucent area without lung markings peripheral to the region of normal ,,,
collapsed lung. A tension pneumothorax is seen as a marked deflation of
the ipsilateral lung with varying degrees of mediastinal shift (caused by air
being drawn into the pleural space but unable to escape). Displacement of
the trachea and apex are L"ldicators of mediastinal shift.
A pneuinopericnrdium is seen as a ~ line of air lining the pericardium, but
If the line continues upwards into the neck folloVving the borders of the
mediastinal structures then it is called a pneumO!;nediastin~.
Causes of a hemithorax white-<~ut are: unilateral pneumonia, collapse of the
lung, pleural effusion (including ~lood-haemothorax or chyle-<hylothora.x)
and tumour.

lbi!Ii¢gi~C!!-~·1!1fli:t~3D#~U~Z!J,•~uD:·~t····- ''•
. "( - ~~·
~
.•
.'· '
~ . '
.

C:iratory distress .
._piratory distress in the newborn is a common problem (see Table 3.2). It
plllenls with tachypnoea (> 60/min), nasal flaring, intercostal recession,
npiratory. grunt, cyanosis.and poor feeding.
A special mention should be made here regarding the respiratory distress
10metimes seen in infants born to .diabetic molllers. The possible causes
Include: (a) many ·b abies are macrosotnic and more likely to be delivered
by c~esarean section with its attendant risk 'of transient tachypnoea of the
newborn (TIN) increase; (b) respiratory distress syndrome is more com-
mon in these babies; {c) .persistent fetal circulation; and (d) polycythaemia-
lnduced stiffness.of the lungs.
Congenital diaphragmatic hernia should be remembered as a cause of respi-
ratory distress at birth especially if the question mentions that the mother
had had no antenatal care (antenatal scans will usually pick it up). It is
caused by failure of closure of the foramen of Bochdalek (posterolateral
position). It is most common on the left because of the presence of the liver
on the right. Hypoplastic lungs result from herniation of abdominal con-
tents through the patent diaphragm compressing the ipsilateral lung (and
'?metimes contralateral lung).. Further respiratory and cardiovascular
compromise occurs after birth as a result of air entering the intestine (espe-
cially so if the condition is not suspected, and the paediatrician uses rou-
tine resuscitativ-e measures such as ·bag and mask ventilation). The baby
rapidly develops acidosis and pulmonary hypertension worsens.
O ues in the clinical examination include a scaphoid abdomen, reduced
breath sounds and reduced chest movement (in fact bowel sounds may be
heard in the chest). Heart sounds may be displaced. Occasionally the
presentation is delayed· and babit:S pr~t wi~ . epis9d~ o.f breathless-
ness especially after feeds and intermittent bowel :Obstruction (such as col-
Icky pain or vomiting) or as a dextrocardia. CXR appearances include tra-
cheal and mediastinal shift, bowel in the chest, and sometimes a cystic
appearance which may resemble a cystic adenomatous malformation or
•taphylococcal pneumonia (and possibly <:ongenital lobar emphysema). '49
Table 3.2 A comparison of the causes of neonatal respiratory distress
Differential diagnosis Features to look for in a question relating to l
of neonatal
respiratory distress
respiratory distress in the newborn
II
I
Respiratory distress Begins within 4 hours of birth. Risk factors:
syndrome (RDS) prematurity, asphyxia. hypothermia, acidosis,
lecithin/sphingomyelin ratio< 2:1._ _ _
c; Sepsis/pneumonia More likely if there has been prolonged maternal rupture
> of membranes, offensive liquor (green liquor is assod5!!tad
-~ with listeria as is the passage of. meconium by a preterm
:J baby). maternal pyrexia, cuttu..e..positive v~inal swabs.
U)
The neonate may appear shocke<J, hypi)tenwe:· hypotonic.
<( acidotic or may develop apnoea and temperature
instability. The white cell·count may be elevated or
E depr~. Thromboc:ytopenia commonly accompanies
~ sepsis In neonates. I~
w Meconium The baby is mature or post matwe and there has
u 'aspiration t?een meconium-stained liquor. Then! may be a t>istory of
·c
.... syndrome intrapartum asphyxia. At birth meconium may .•dve been
I!
.~ visualised beyond the vocal cords. Hyperexpz~nded chest.
-c Meconium-stained liquor of long standing may cause
CD staining of the skin and nails (possible slide question).
«S
0.. There may be a history of a traumatic delivery. look for
other evidence of birth trauma. Hyperresonant
hyperexpanded asymmetrical chest. History of ventilati~n
(perhaps·over-vigorous resuscitation, high PEEP). t-
PneumothOI'Cill occurs spontaneously in about 1% of all
deliveries. Remember phrenic nerve palsy$ a cau~ of ·
respiratory distress following a traumatic birth <diagno'Sed
·by fluoroscopic v~'tion of diaphragmatic movement II
or ultrasound ~ere the paralysed side moves upwards on II
inspiration (called paradoxkal movement).
Congenital heart Usually presents after the first 12 hours. Look for
disease signs such as cyanosis. large liver, murmurs c.r abnormal
put~. May be history of maternal illness during
pregnancy (maternal rash or fever or drug ingestion},'
Pulmonary History of birth asphyxia, cardiac failure, pneumonia,
haemorrhage bleeding diathesis and in ·some babies the administration
of some types of surfactant. History of blood (often pinK
and frothy) coming up from the mouth or endotrachec~J
tube).

Ideally the baby should be intubated before any inspiratory effort.


Manage with the head upright, an.d using nasogastric suction in an
attempt to deflate the intestines. Resuscitate with fluids and correct the
metabolic acidosis. Pulmonary hypertension may occur and pulmonary
vasodilators -such as prostacyclin, tolazoline or nitric::' oxide should be
employed to treat it. High frequency oscillation may also be used. When
the baby is stable refer to a surgical centre for repair of the hernia.
- Do not forget the association of 'wl1ooping cough and a lymphocytosis (a com-
50 mon data case). The ques.t ion may describe the classic three-phase history,
the most characteristic of these being the paroxysmal phase with parox-
yams of coughs followed by a whoop in an older child. There may be large
•mounts of thick mucus production. Vomiting and choking attacks after
the paroxysms are characteristic. Subconjunctival hae~orrhages and peri-
orbital petechiae are often seen in children with severe disease.
Lymphocytosis (often> 70%) is more common in children over 3 years of
age. Other complications include bronchopneumonia, bronchiectasis
(often reversible), otitis media, convulsions (in infants more commonly)
and cerebral haemorrhage with resulting mental retardation. Because of
the chronic nature of the cough a rectal p rolapse or umbilical hernia may
be precipitated. Culture of the organism Bordetella pertussis can be carried
out using a per-nasal swab. A lternatively IgG and IgM serology can be per-
formed. Prophylaxis is with immunisation and erythromycin may be given
(although though~ to be most effective in the initial catarrhal stage).
You may be described a history of a baby who develops respiratory distress
and possibly cyanosis shortly after birth. He is intubated and ventilated but
has minimal ventilatory requirements. On extubation the baby again devel-
ops respiratQry distress. Alterr.atively, the history may describe an improve- .
ment m :symptoms when the baby is crying. These descriptions should lead
you towards considering choanal atresia as a possible cause. Babies are nasal
breathers and choanal atresia thus poses a particular breathing problem for
lhem. It is most easily diagn~ by passing a feeding tube up each nostril.
~rt a Magill airway (or intubate) until surgery can be carried out.

lome q uestions test whether you can make a connection between respira- ·
lory symptorn·s such as cough, wheezing and dyspnoea and a microcytic
hypochromic a11aemia. Of course the two could be unrelated, with respiratory
aymptorns caused by asthma for example and the anaemia a result of poor
ftutrition. However you should also consider primary pulmonary
haemosiderosis (which is sometimes associated with cow's milk intoler-
Ance and later on in life with Goodpasture syndrome). It is caused by
repeated episodes of bleeding into the lung tiss1.1e with deposition of
haemosiderin leading to progressive fibrosis. Additional symptoms may
Include haemoptysis with coughing up of rusty sputum: A CXR may
r.veal patchy shadowing caused by the presence of alveolar infiltrates.
lronchoalveolar lavage may help in the diagnosis by finding
haemosiderin-filled macrophages. Treat with cow's milk protein free diet;
ltansfusion and steroids may be of some help.
There are questions that relate to a child with Marian syndrome who pre;.-
tnts with sudden onset of chest pain. The .possible causes are: (a) pneu-
mothorax; (b) aortic dissection; (c) any other cause ;:>f chest paul nDt asso-
llted with Marfan syndrome.

ldor
~ •'mnrnonpaediatric problem is the child with stridor. Clues from the Nsto-
ahould help you limit the differential diagnosis (see Table 3.3). Stridor is a 51
Table 3.3 Comparison of the caus.e.s of stridor
Cause of acute stridor History Management
Acute Commonest in 1-3-year Cool steam mist vaporiser
taryngotracheobronchitis age group. may case. breathing.
(croup) Parainfluenza virus Careful attention to
most common cause. fluid balance.
Onset over a couple of Steroid nebuliser.
-~ days with coryzal
symptoms. Mild fever.
· Adrenaline nebuliser may
help buy time befo·re
·~ hoarse voice. barking transferring to intensive
cough and inspiratory care but should only be
::J
f/) stridor. worse at night. used as a rescue rather
than as regular treatment
ct
.. because of its short-lived
action and possible
Eeo worsening ,o f stridor wher
>< effect wears off.
w Intubation is needed in

-u
·;::
.!2
'"C
' Q)
eo
Acute epiglottitis
age group.

type B is causative
about 1% of cases.
Commonest in 2~ year Do not· examine the
throat. Nothing should bt
Haemophilus influenzae done to agitate the child
since this·may precipitate
ll. agentandresuhsin complete obstruction (thu
rapid swelling of the no i.v. cannulation etc). AI
epiglottis and atmosphere of calm is ve'\
aryepiglottic folds important. Summon an
caosing high fever experienced ENT surgeon
(>38.5"0. The child {ef11ergency tracheostomy
toolcs toxic. and is may be required at any
drooling with a wealt time) and anaesthetist
muffled voice. urgently; nebulised
Coughing is rafe,' adrenaline may be given I
patient adopts position the meantime. Arrange fo
with neck·extended intubation of the airway
leaning forward. Lateral ideally in an intensive cart
neck X-ray shows an setting (when direct
enlarged epiglottis laryngoscopy ~o confirm ••
resembling a thumb. inflamed cherry·r~
epiglott.iJ can al$o be
carried out). Once
accomplished i.v.
antibiotics should be
given. e.g. cefotaxlrne.
Extubate after 1-2 days.

52
-r '~able 3.3 Continued
C•use of acute stridor History Management
lecterial tracheitis May follow on from Similar to management of
croup-like illn~s with epiglottitis since the latter
I
infection by cannot be completely
Staphylococcus aureus. excluded and presentation
The 'croc.tpy child' fails can be similar. Intubation
to improve and Is usually necessary. Intra-
develops a high fever venous anti-staphylococcal
I
and becomes toxic, with antibiotics should be given
a productive cherty after tracheal secretion
cough and stridor. swabs have been taken.
1 Diphtheria Coryzal symptoms and Vaccination as prevention
sore throat are (Schick test checks
followed rapidly by the immunity to diphtheria).
J . development of a
pseudomembrane
For disease itself give
antitoxin and antibiotic
(grey/white) which (erythromycin or
causes airway penicillin). Management of
I
obstruction. The airway obstruction.
bacteria responsible is
Corynebacterium
diphtheriae. Release of
a toxin results in carditis
in week 2 (with tachy-
cardia, heart failure),
respiratory failure
.
(secondary to diaphrag-
matic paralysis), palatal
paralysis as well as limb
paralysis in we~!ts 3-8.
Inhaled foreign body Always suspeq(il\haled X-rays (AP + lateral) may
foreign body if the help localise the foreign
history describes an body if radio-opaque
arute episode of and identify hyperinflated
choking or a sudden lobe/collapse. In addition,
bout of coughing. The an urgent rigid
child is usually less than bronchoscopy under
4 years old. You should general anaesthetic should
be aware that It may be performed in order to
take several days before localise and remove the
the features of a object. Remember that
pneumonia may develop. small objects have a
Also suspect if there is . predellctlo!' for the right
unresolving pneumonia... main bt-onchus.
or bronchiectasis. On the
other hand It may be
immediately obvious
by the presence of
coarse stridor, fixed non-
changing wheeze. aphonia,
collapse or overlnflation
of a lobe depending on
the site of lodgement
of the body.
53
u
noise made during inspir<~tion as a result of airway obstruction above tJl
level of the thoracic inlet (obstruction in the subglottic area may produ(
some expiratory noise in <1ddition). Obstruction occurring below the thorac
inle t results in narrowing of the airways mainly during expiration and resul
in wheezing.
Other aetiologies that you should be able to list as causes of acute strid~
include: retropharyngeal abscess (toxic with neck extension and cervic4
lym phadenopathy) treated with incision under general anaesthetic ani
antibiotics; angioedema (following anaphylactic reaction or rarely in hered
tary angioedema); and following burns to the neck and laryn
Hypocalcaemia is a rare cause in the neonatal period.
Remember that severe upper airway obstruction may not uncommonf
result in acute pulmonary oedema which is thought to be brought about~
the negative intrathoracic pressure resulting in the responsible hydrostal
changes.
You should be able to discuss the causes of chronic stridor (see Table 3.4
ImJestigations of a child with chronic stridor consist of the fol' .·:;ng: ch
X-ray (PA and lateral), neck. X-rays, barium swallow, CT scan, MRI scan
possibly direct visualisation of the upper and lower airways using flexib
laryngoscopy and bronchoscopy. TracheoffiQlacia on bronchoscopy loo
U-shaped (instead of the usual circular shape) and collapses during expit
tion as a result of the lack of the cartilaginous rings ·e ncircling the majority
the tracheal or bronchial circumference.
- Vasc11lnr rings should always be considered in the differential diagnosis 1
unexplained stridor, wheezing or cough, dysphagia or feeding difficulti
in children. They result from congenital abnormalities in the main arteril
in the thorax that cause compression of the _trachea or oesophagus resu
ing in the abo,·e symptoms. R.htgs may be complete, that is complete
encircling the trachea, usually producing more severe symptoms (e{
a double aortic arch) or incomplete, that is incomplete encircling wh~
symptoms are less severe, such as anomalous innominate artery. Diagn~
is confirmed by CXR, barium swallow, echocardiogram, bronchogra~
endoscopy, angiography and MRI. Oearly not all of these are necessal
but it is not uncommon that the diagnosis will be picked up incidentally l
using one of these techniques in investigating the presenting symptorr
Treatment is surgical. Remember that the long-tenn compression of tr
cheal structures may result in tracheomalacia or bronchomalacia whl
may persist postoperatively.
- A b~by who has had a tracheo-oesophngeal fistula (TOF) repair in the p
may have the following problems (essential knowledge for a possible Ion
or short case): anastomotic leaks; strictures at the site of anastomot
1: I (which may require intermittent balloon dila~tion); gastro-oesophag
reflux; and commonly respiratory symptoms such as recurrent cough (f0
cough), bronchitis and pneumonia. ·
\ '!
- It is possible that you may face a history of a l1ypersens itit•ity pneuma#
tis which is caused by inhalation of a type of organic dust, called extrl
54 sic allergic alveolitis. It is thought to be caused by a combination of ty•
~~---------------------------------------------------------,
1
Yable 3.4 Causes of chronic stridor
~a.yngomalada The larynx is small with floppy aryepiglottic folds. It
appears in the f irst month of life: mainly insp~ratory
stridor but some also demonstrate expiratory as well.
The <hild grows and develops normally. The stridor
appears worse when the <hild is supine, has an upper
respiratory tract Infection (URTI) or is agitated and
crying. Improves spontaneously by age 1-3 years.
tubtllottlc stenosis Stenosis just below the level of the cords. May be·
congenital or acquired (secondary to repeated or
prolonged Intubation. inhalation of noxious fumes or
bums). Stridor worse if agitated. crying or intercurrent
URn. As the child grows the stenosis gets less severe.
This may result from more central CNS lesions or more
peripheral lesions such as recurrent laryngeal nerve
palsy secondary, for example, to intrathoracic
pathology.
c.mptesslon leading Examples include subglottic haemangioma (look for
• obstruction cutaneous haemanglomas that may also be present),
(Intraluminal, luminal cysts. compression of airways by vascular rings,
lAd eXltalumlnaO laryngeal web, laryngeal papillomatosis (caused by HPV
infection sometimes transmitted vertically via birth
canal), retrosternal goitre, neoplasia and cystic
hygroma.

, and 4 hypersensitivity reactions. Previous sensitisation is necessary


lnd following re-exposure to the antigen the child develops fever,
cough and dyspnoea (usually 8-12 hours after contact with the antigen).
rackles may be heard on auscultation but wheezing does not occur in
tht majority of cases, and symptoms disappear after a few days.
01inophilia is unusuaL A chronic form occurs after severe repeated
ICUte attacks, with pulmonary fibrosis, widespread crackles, dyspnoea
on exertion and eventually respiratory failure (type 1) and cor pul-
monale. lnitia.l CXR features show patchy infilt•ates leading to micro-
nodular shadowing and later to honeycomb lung. Transfer factor is
llduced. Diagnosis is also aided by estimation of precipitating antibody
levels to the suspected antigen. Treatment involves prevention of aller·
pn exposure and steroids may help reverse early ~isease. Examples
Include: fanner's lung (exposure to mouldy hay- Micropofysporafaeui),
ltlrd fancier's lung (exposure to bird droppings which contain serum
IVlan proteins).
UteS of pulmonary eosinophilia (combination of peripheral blood
IOilnophilia and eosinophilic lung infil~ates usually resulting in CXR
lhadows, confirmed by bronchoalveolar lavage or lung biopsy) include
fungi (e.g. Aspergillus fumigntus), drugs (e.g. sulphonamides, NSAlDs,
lltracyclines and nitrofurantoin), parasites (ascariasis and schistosomia-
•ta), vasculitides (e.g. Churg-Strauss syndrome) and idiopathic causes. 55
-Some questions with a respiratory slant ~y make use of the hy
traemia caused by SIADH (syndrome of inappropriate ADH secretion
occurs in some respiratory illnesses, for example an acute-,as.t hina a
pneumonia or following ventilation.
- Some questions give a history of a child - a few weeks to a few mon
age - who has had feeding problems since birth, in particular ch
bouts during feeds, vomiting and recurrent aspiration and chest infec
Intercurrent CXRs are normal and the baby appears to be growing
developing normally. In addition the question may also give you a h"
of apnoeic episodes (even in the absence of the above sympto
Immediately you should think of two particular diagnoses to exdud
gastro-oesophageal reflux, excluded by a pH probe or barium stu'dy; (2) H
tracheo-oesophageal fistula (5% of all TOFs) which can be difficult to dia
by p lain X-ray films but can be seen with a contrast barium swallow.
-The causes of lung fibrosis include sarcoidosis, extrinsic allergic alveo
congestive cardiac failure, ifibrosing alveolitis, pneumoconios;- ..,rcoi
and drug reactions, for example busulfan, amiodarone, nitrofurantoin
methotrexate.
- Haemoptysis is fairly rare in children but could present as a grey case.
differential diagnosis includes: cystic fibrosis, pneumonia {including p
mococcus and TB)~ foreign body inhalation, bronchiectasis, blee.
diathesis, idiopathic haemosiderosis, vasculitis (e.g. Wegener gran
.
matosis), arteriovenous fistula and ruptured hydatid cyst.
-You may-come across allergic bronchopulmo11ary aspergillosis (ABA). It oc
in long-standing asthmatic or cystic fibrosis patients as a result of an a
gic reaction to Aspergillus fumigatus (type 1 and 4 hypersensitiv·
The child will usually be in his 5econd decade. Following sen.sitizatio
the antigen, additional exposure to the antigen causes a hypersensith
reaction which results in recurrent episodes of fever, wheezing. crep
tions and breathlessness with transient migratory pulmonary infiltr
manifest on the CXR as shadows on the lung fields. Subseque
bronchiectasis develops (especially of the proximal airways) followed
progressive fibrosis. Investigations include: a full blood count wh
demonstrates the typical blood eosinophilia (also present in the spu
increased serum lgE levels; serological te~ts for precipitating antibodies
Aspergill11$ jumigatus ·as well as a positi~e skin test to it (wheal and fla
reaction). There a re other .pulmonary eosinophilias but ABA is the COl
monest. Avoi~ance of the antigen is impossible and the mainstay of tre;
ment involves the use of steroids and bronchodilators. lgE levels fall wi
successful treatment. Other diseases caused by Aspergillus include ,
aspergilloma forming in a lung cavity (may result in severe haemoptys
and invasive aspergillosis.
-Bronchiectasis may be described in a question setting as a child who ha:
chronic productive cough with purulent sputum, halitosis, recurrent ch•
infections, episodes of haemoptysi~ (from a bronchial artery and thus s~
56 temic and not pulmonary blood) and clubbing. Coarse crackles and wheezi
are hear~ on auscultation. CXR appearance shows typical tram lines
caused by dilated bronchi in the affected lobe, including areas of fibrosis or
t\•idence of the causative problem, which may be: (a) obstrliction (e.g. an
unrecognised foreign body); (b) seyere viral infection (e.g. adenovirus,
measles .or pertussis); (c) allergic respiratory disorders such as allergic
bronchopulmonary aspergillosis; (d) inherited disorders such as cystic
ftbrosis or Kartagener syndrome; (e) in immunodeficiency syndromes.
~n is considered only for localised disease.

You should of course be familiar with the connection between cardiac


disease and mpiratory symptoms. Cardiac failure may cause respiratory
ayrnptoms such as shortness of breath, wheezing, tachypnoea and bilater-
al fine crepitatiol)s on auscultation. In addition the presence of cardiac fail-
we with pulmonary oedema predisposes to recurrent chest infections.
Right-sided heart failure may cause respiratory symptoms as a result of the
development of pleural effusions. Also remember the fact that respiratory
diseases may cause right-sided heart failure secondary to chronically
raised pulmonary hypertension (cor pulmonale).
The causes of a bell-shaped chest include: pulmonary hypolasia, Jeune's
u phyxiating thoracic dystrophy, Werdnig-Hoffmann disease and bulbar
palsy.
You may be faced \Vith a question relating to the oxygen dissociation curve
In the viva.- Remember the' factors that shift the curve to the right (that is~
the Hb releases c>xygen more easily but is less good at taking it up):
Increased PC01 (mainly by an effect on pH - the Bohr effect), decreased ·
pH, increased temperature, chronic hypoxia, anaemia, increased red cell
2,3 DPG (an end product of red-cell metabolism with increased production.
In chronic hypoxia, e.g. high altitude or chronic lung disease), HbS and , :.
polycythaemia. Factors that shift the curve to the left (good at taking up
oxygen but less good less at giving it up)· include: a decrease in PC02,
Increased pH, decreased temperature, metHb,. carboxy Hb and HbF.
The causes of pectus· carinatum inc~~:~de: Morquio syndrome, asphyxiating
thoracic dystrophy, rickets and chronic respiratory problems such as
obstructive airways disea~ · · ·

ICertagener syndrome
ICartagener sY-ndrome (~tile cilia syndrome) is a fav~~te .exam topic.
U the name suggests it .is a disorder of cilia function and thus affects the res-
l'lratory .sy~tem. (~ well as sperm in. mate_:>_
). It is inherited in an AR fashion.
ba should· ~ ~~rted to the possibility..~y 'chfonic recurrent chest infections,
as
IWCUrJent sinus infections (that may masquerade facial pain or headaches),
wei ~d sinus polyps, recurrent otitis media, bronchiectasis, .dubbing and
lftlle infertility. Remember that these features are also features of cystic fibro-
tll (but note·that in I<artagener there are no gastrointestinal features). In addi·
ttDn to these features, situs inversus occurs in about 50% of patients (you may
Ill shown a CXR of dextrocardia in the clinical examination or o~ a slide). 57
Skull X-rays often show absent frontal sinuses. The diagnosis i:; made by elec-'
tron -microscopy ot cilia obtained from nasal brushings j.n which structural
abnormalities in the dynein arms of the cilia are demon~frated. Treatment
involves management of the bronchiectasis and it is the rate ~£.progression oil
(I)
bronchiectasis which determines the overall prognosis. .
:'2 Your list of causes of recurrent pneumonia and persisting pneumoni~
:::J
(!) should include: cystic fibrosis, Kartagener syndrome, gastro-oesophagea
c; reflux, bronchiectasis, immunodeficiencies, foreign body'.a.J?d stritctutal air·
.::: way defects (these last two especially, if recurrent.at~cks are' in the sam~ lobt'
i! or lobes). Disorders giving rise to recurrent aspiration (such as bulbar pa-lsyl
:::J and resistance of the ?rganism to the antibiotic used are additional causes.
t/)
<(
.. Pneumonia I

E
cu Pneumonia i- common in clinical practice and you shoul~ know some of th!
><
w characteristics of the more prevalent ones (see Table 3.5).
0 NB Haemopllilus influmzne and Str~. pueumomae are encapst. ,lted}t}rgan

.....
'i:
isms and septicaemia from these organisms as a result of seetling ·ho~ ~
~
"0
(I)
cu
Q. ._.;,"(~'

Table 3.5 Comparison of the commoner organisms causing pneumonia 111 ip


paei:tiattic populations
Organism Distinctive features
~umococc:us (Strep. From 2 months of age and throughout childhood.
pneumoniae) Commonest cause of bacterial pneumonia. Patchy
consolidation in younger children and lobar pattern
in older children (commonest cause of lobar
pneumonia}. Small pleural effusions may occur. Rusty
sputum Or haemoptysis.
Haemophilus influenzae From 1 month and throughout childhood but most
typeB common in under fives. Less prevalent.·now as a
result of immunisation. Most commonly lobar and
less commonly bronchopneumonia. l.ess acute
presentation than pneumococcus.
Mycoplasma pneumonia From 3 to 15 years (most common in 10-15 year-
olds). Gradual onset of symptoms. Cot,.~gh, fever,
headache, chest pain, sore throat are,common and
crepitations are heard in most. CXR,t\ighly variable but
usually unilateral (often looks ~ than ~finical state
of patient). tower lobe brondlopneumonia is most
common and Mar tym~~l:Xcur$·in one-
third. Associations: croup,bronchiOtifli 'otitis media,
b.ullous myringitis, n'ief)i~~ •811hropathy 1
and rashes. especially erythema tnu~rme:1 Positiw
Coombs' test wtth cold agglutinins in 50% of cl'lses,
some with haemolytic anaemia ~ping, diagnosis
is by finding rising antibody titre (x 4 rise in ·
2-4 weeks). wee is usually normal. 1
58
,..,. 3.5 Continued
Olganism Distinctive features
ttlph. au~us Most common in infants, also in
immunocompromised children (remember chronk
granulomatous disease as a cause), tracheostomy
patients or prolonged intubation, post influenza and
cystic fibrotics. Areas of patchy consolidation give
rise to cyst and abscess formation (the result of
tissue necrosis). air levels may be present in the cyst
and give rise to the characteristic pneumatocoeles
(Klebsiella, Pseudomonas, foreign bodies and T9 may
also cause abscess formation). Pneumothorax and
empyema may result from abscess rupture.
~Nt tnchomatls Seen In infants up to about 3 months of age. It is
acquired during delivery as the baby passes through .
the birth canal (up to SO% risk of transmission).
Conjunctivitis is the most common presentation. The
cough is described as a staccato pertussis-like cough
with fine crepitations and an eosinophilia (in an
apyrexia l child). There may be a history of a
conjunctivitis in preceding weeks or It may coexist-
CXR shows interstitial infiltrates. Diagnosis is by
chlamydia! swab from the eye (Giemsa stain showing
chlamydia inclusion bodies in epithelial cells} and
rulture as well as serology. Treat the parents since
infertility Is a common compli~tion.
Influenza virus From infancy and throughout childhood. Typically
with accompanying bronchitis and bronchiolitis.
Genera l malaise and coryzal symptoms. CXR shows
interstitial pneumonia and peribronchial thickening
(as with all viral pneumonias}.
"'•lnftuenzae Most -commonly associated with croup but may cause
similar picture to influenza.
llllplratory syncytial Commonest cause of bronchiolitis and common
wiM(RSV) cause of pneumonia. Late autumn and winter. Half
of all infants will acquire RSV infection in their first
winter. Fever, cough, wheezing bilateral crackles
throughout both lung fields. hyperinflated chest.
CXR may show bronchopneumonic changes.
,._.,mocystis car/nil
CKP)•
lmmunocompromised children. Children in the
first year of life may present with a chronic slowly
progressing afebrile pneumonia. Bronchopneumonia
or lobar involvement- CXR usually diffuse bilateral
midzone alveolar shadowing (often looks worse than
dinkal findings). In older children cough, dyspnoea,
tachypnoea. Intercostal recession and possibly
hypoxia and cyanosis are prominent features. Some
HIV positive infants present in the first few months
of life with a bronchiolitis·like syndrome but are RSV
negative (but positive for PCP).
t;'Winii has re<ently been renamed P jirove<i: however the P. carlni1 (PCP) terminology may
flllllln In use for some time yet.
59
(
I
pneumonia are more likely in splenectomised patients (e.g. post sp>leneclom) ,,
sicklers) and immunocompromised patients (such as those with AJDS).
A child who has recurrent pneumonias which are slow to resolve may haV)
bronchiectasis, obstruction of lower airways arising from any cause, preseno
(I) of a foreign body, cystic fibrosis, cilia dysfunction, gastro-oesophageal reflu~
:2 cardiac failure with pulmonary oedema or the organism is not sensitive 1o thl
::l
C) antibiotics used (see above). Neuromuscular disorders with bulbar palsy mal
have aspiration with recurrent chest infections. Pneumonias caused by Stap_!r) I
C'G
> Klebsi~llil. and TB frequently cavitate.
·~ You may be presented with an immunosuppressed child who develops
j cough with shortness of breath. The likely possibilities include PCP pneum<1
U)
nia, atypical pneumonia, measles giant-cell pneumonitis (a type of pne~,,
<(
monitis that occurs in chlldren.with poor cell-mediated immunity) or an
E other type of pneumonia.
C'G
)(
w Tuberculosis

-
u
·.::
.~
"C
(I)
C'G
Tuberculosis is on the increaSt' and thus a question topic. lt is much r..ommon
in the Asian population. Know a little about its natural history. Primary W
tion via i.."lh.alation of tubercle bacilli results in the Ghon focus (1- 2 on in d.iam
eter) which is subpleural and mid-zonal in position. The bacilli spread to
0..
mediastinal and hilar lymph nodes to cause inflammation (caseous), b
immunity develops quickly confining the lesion; together ""ith the Ghon ~ 't
this forms the 'primary complex'. The prim~ lesion may be extrapulmona
1
in 25o/o of cases. Fibrosis or calcification may occur. Secondary or post-primati, •
TB involves reactivation or reinfection with TB. These lesions tend to be in tif
posterior segment of the upper lobe or ·a pex of the lower lobe (parts where aet
ation exceeds blood flow). Cell-mediated/type 4 hypersensitivity reaction tak U
p lace. In most people these lesions heal leading to calcified apical sea
(Assman focus) but in a minority the disease spreads and ~aseating granulom~
result in lung tissue necrosis leaving fibrotic and distorted lung tissue behind
This process results in haemoptysis ahd haematogenous spread and may resui
in miliary TB or in single organ involvement such as the CNS. urinary trac~
bone or lymph nodes. Miliary TB may occur in primary or post-primary TB an~
the risk is greatest in the first year after infection, before the age of 5 years and
a fter puberty. Pleural involvement may result in a tuberculous empyema.
Clinical features will be dependent on the site affected.

Diagnos~.

-Microbiological: Ziehl-Neelsen stain for add fast baciUi or culture 01


Lowenstein-Jensen medium. Gastric washings, early morning urine spe~
imens and sputum if the patient is old enough provide sources.
- Radiological: Look for evidence of cavitating, calcified lesions.
-Immunological: Tuberculin test: Mantoux: Following intradermal injectiQI
of tuberculin (0.1 ml of 1 in 1000 strengt.'l PPD) cell-mediated response !
read at 72 h. A positive response is induration (not just erythe ma) at the sill
60 of injection of more than 10 mm (< 5 mm is negative). A ~itive reaction
(which may take 4-6 weeks to develop post infection) implies infection but
Immunity, that is previous infection or BCG, may also cause a positive test,
lJ ollthough unlikely to produce indt~ration of > 10 mm (especially if 3-5
years following vaccination). If there is a large induration > 15 mm this
v, makes active infection more likelv (even if low risk). A 5-10 mm wheal
cr with an appropriate contact and cJWcal history should warrant a CXR and
11
,.peat test in 6 weeks' time (an intermediate response such as this may be
~a) lhe result of previous BCG or atypical mvcobacterial
,
infection).
h lf/stological: Caseating granulomas seen. Also stain for acid-fast bacilli.
Hnematological: ESR raised. If chronic, anaemia may develop.
•Q l'rrtltment: Asymptomatic primary complex: isoniazid for 6 months-1 year.
'' aymptomatic pulmonary disease 2 months' rifampicin, isoniazid, pyrazi-
l n\lde and ethionamide and 4 months with rifampicin and isoniazid. Longer
rlod of treatment is needed for extrapulmonary diseaS('.
II a baby is bom to a mother with TB (PPD positive) one should initially
Jlrate the baby from the mother and the baby should be given prophylaxis
llh Isoniazid for 3 months; the tuberculin test and CXR should then be per-
fmed (BCG vaccination is also given by some). Isoniazid should also be
lvtn tQ those babies at risk of con tact with infected individuals.
ICG is approximately 80% effecth·e when given to teenagers and even
,. protective when given to babies. in the first year of life, when it protects
1lleially against miliary TB, TB .meningitis and severe lung involvement.
ehould especially be offered to black and Asian babies.
A folse negative tuberculin test may be the result of immunosuppression.
l lftutrition or severe widespread TB.

ltltrential diagnosis
ltrrcoidosis: This is rare in children but may be the basis for a grey case
jUtstion. It is a non-caseating granulomatous disease which can affect any
ptrt of the body. It is most often seen in adolescents. Thoracic disease con-
lata of bilateral hilar lymphadenopathy or may cause parenchymal lung
dlloase with cough and dyspnoea. Skin signs include erythema nodosum,
llUr Infiltration, raised nodules and lupus pernio. There may be gener-
AIIMd lymphadenopathy and hepatosplenomegaly. Eyes, heart, kidney,
t•lhaltary gland, cranial and peripheral nerves may also be affected.
Investigations include histological examination of lymph node biop-
ltH. Bronchoalveola r lavage shows a high proportion of lymphocytes.
"" J<veim test is analogous to the tuberculin test in method but employs
r~old spleen as the antigen. A positive reaction (granulomatous
M ponse within 6 weeks) strongly suggests sarcoidosis. Tuberculin test is
ftl. . tive. Hypercalcaemia, eosinophilia, serum ACE (reflecting disease
I Uvlty) and immunoglobulins may all be elevated. Pulmonary function
IN ti sho~ a restrictive pattern and reduced diffusing capacity.
l 11untaneous remission may occur and active disease is treated with
lt mlds. 61
- Atypicolmycobnctain: There are several types of organisms in this categ~ I
but Mycobacterium m.oiwu-intracellulare is the most common in the Weste
world. There is nt.' histl)ry of t?xposurc to TB and the child pre~nts willi iTI
unilateral hatd non-painful swelling (lymphadenitis) most commol\
Q)
affecting th~ submandibular and cervical regions. Rarely lung dise<( I
·-::s
"C

(!)
resembling TB may occur and widespread disease is a feature of inunun 1
compromised patients such as those with AIDS. Diagnosis is by biopl
c; histology and culture, and treatment involves surgical removaL
.~
'::s= Asthma
U)
<( Differential diagnoses of asthma include: viral~induced wheeze, cystic fibt
sis, inhaled foreign body, heart failure, post-infectious wheeze, recurrent a5f
E
C'O
ration due to gastro-oesophageal reflux, airway compression caused by a ' }\
>< tumour, adenopathy and cardiomegaly. immunodeficiency, J<artagene1· s~
w drome, congenital lung disease (as described above) a:nd bronchomalacia.

-u
't:
.~
"C
Q)
C'O
Cough, wheeze and shortness of breath are the hallmarks of ~ ·.!1:na. PEl
readings are a possible data q1..1estion and you should be familiar with son
commoner patterns such as the PEFR moming dipper, or reduction of PEP
by more than 15% following exercise challenge which may be reversed l
bronchodilator administration.
a.
A typical CXR during an asthmatic attack shows hyperinflated -lung fid
with flat diaphragms and increased bronchial marking$.
Some children present with a troublesome nocturnal cough w ithout at
wheezing (common outpatient dilemma). These children may have pot
nasal drip syndrome, asthma (espedally house dust mite allergy-re!at!
exacerbations), sinusitis, inhaled foreign body, immunodeficiency or cysl
fibrosis.

There are several chronic stable paediatric respiratory diseases and these c~
ditions are highly likely to be called up in the clinical examinations. With tl
respiratory system you will have to tailor your examination to the age of t1
child: a number of exa mination procedures in the older child will not on ly I
extremely difficult to perform in the younger child but more often than 111
will be uninformative.
- Introduce yourself to the child and paren~.

-Undress the child's top half (to the waist) and stand back. Ideally the chll
should be at 45• and in the case of a baby on his back or in whatever pOl
tion the infant is most comfortable at rest.
-Inspection: The younger the patient is the more important this part o f th
examination. ls the child in respiratory distress? Is the child using 1),
accessory muscles of respiration? You should measure the respiratory r1!
(over 10 s and multiply by six for 1 min). look for dysmorphic featun<
does the child look well/unweH, is he thriving? Are there a ny structuh
62 chest deformities (p~tus excavatum/carinatum) or chest expansion? LOI)
•q lur abdominal wall movement. since children under the age of 5 years are
;e tUentially diaphragmatic breathers and thus increased abdominal mo\·e-
tl rn\•nts imply increased n•spiratory dfort (in addition to l)tht.•r signs).
Jll Look for Harrison's sulci (e,;dence of long--standinf; respiratory dis-
ea lnrls), cyanosis, nasal flaring, pursed lip breathing, tracheal tug, oxygen
J.J1 administration, intercostal recession or scars (from previous surgery, chest
·~ drain or tracheostomy). Look all round the chest including under the axil-
lat. If you suspect cystic fibrosis, glance at the abdomen looking for t'\'i-
lltrtce of bowel surgery for a possible previous meconium ileus. LOok for
htatures of Cushing disease (as a result of steroid therapy for the respira-
tory disease). Look for the presence of haemangiomas in the presence of
br atridor, Listen for any audible breathing noises such as w heezing, stridor
.sr ur cough.
:~fake both hands and look specifically for clubbing, anaemia, cyanosis and
;)f
tmnor (ask the child to hold out his hands to look for the fine tremor of
EJ N lbutamol administration or with their fingers widely separated for the
){ O.pping tremor of col retention).
a Atk the child to stick out his tongue to look for central cyanosi.s .
t
lxamine the cervical lymph ~odes. At this stage of the examination this is
done from the front, although of course it is ideally performed bimanually
11om the back when the patient is sitting forwards as you auscultate the
back. of the ch~\ (if yo!-l,remember to do it then)'- the reason for doing it
al
now is simply so that you do not forget it.
()j

til ltcamine the trachea by gently putting your index finger in the gap
st bttween the trachea and the sternal head of sternocleidomastoid on each
Nde and seeing if the gap on both sides is equal. Perform this on one side
and then the other to avoid alarm to the child (who may be frightened or
ticklish).
Palpate the apex beat with the palm of your hand feeling for the most
ptripheral point that you can feel the apical heart beat. Define its position
from the sternal angle o/hich corresponds to the second inte.rcostal space.
Depending on whether the trachea or the apex ~tor both have deviated
wtll indicate whether the upper or lower mediastinum has shifted to a
pater or lesser degree.
l11 •m infant: you should leave out palpation and percussion of the chest and
10 straight to auscultation at this po~t:
Ill an older-clrild: you should now palpate the chest. Spread your fingers out
widely and place both your hands on each side of the child's chest so that
yC'Iur fingertips are fixed tight against the lateral parts. of th~ child's thorax
And your thumbs meet in th~ midline over the sternum. As the child
bn!athes your thumb mo~·ements should act as a gauge of chest expansion
nn each ~ide ot the chest.
The next stage of palpation is tactile \'ocal fremitus {TVf). Pla(:e the palms
uf both hands on each side ,,f the chest and ask the child to ;;ay 99. Feel fnr 63
the vibratory sensation in your palms and assess ii i t is equal on both sidt
This should be done on the upper, middle and lower parts of the che
wall. TVF is increast:>d when there is underlying consolidation and reduc(
over a pneumothorax. pleural effusion or area of collapse.
- Now percussion. Warn the chil~ that you are going to tap on his chest ('lil
a drum' many use). Start percussing in the supraclavicular fossa and wo1
->co your way down the chest (top, middle and bottom) comparing right wil
left as you descend. Percuss additionally in the mid-axillary line on eac
-~ side. Hyperresonance is seen in hyperinflation or pneumothorax an
::::s reduced in plE'ural effusion (stony dull), -collapse, consolidation and ovt
f/) the liver and heart. Remember the liver will usually be at the level of tl1
<(
nipples in most cases (sixth intercostal space anteriorly).
E
co -Auscultation: If the child is compliant then ask him to open his mouth an
>< breathe in and out. Show them first and demonstrate how to do this prof
w erly. Usten with your stethoscope to the top, middle and bottom p<~rts of th
0 lung fields and then in the mid-axillary line, comparing rigf, ' and left ~
."C....~
"i:
· each level. At each site listen for one cycle of inspiration and expiration: y01
should be listen,ing for. the nature of the inspiration and expiration. No~
<l> vesicular sounds consist of inspiration and U1e start of expiration with n(
co
0.. break in between. Additional sounds such as crepitations, wheeze, pleur~
rubs, bronchial breathing (the same sound heard when the stethoscope ~
placed over the trachea: inspiration time= expiration time-with a pause ~
between}. Listen for a prolonged expiratory phase as seen in bronchial air
way. obstruction. If wheezing is present, is it monophonic (implyin
obstruction of a single larger airway) or polyphonic {many airways)? l
crepitations are present, are they fine (e.g. pulmonary oedema) or coai'Sl
· (bronchiectasis, pneumonia)?
-Now sit the child forwards. Now repeat TVF and percussion (though th~
two not in an infant) and auscultation over the back in the same fashion Rl
you did over the front. As you come to auscultation use this time for brin~
ing together the clinical signs that you have found.
-Sit the child back again and turning to the examiner say that to comple1
the respiratory examination you would like to perform an ENT examim
tion, measure PEFR (if the child has evidence of bronchial obstruction) ani
plot the height and weight on a growth centile chart.
You may want to feel for a right ventricular heave (at the left sternal edgll
listen for a loud P2 and ask to fuel for liver enlargement and peripheral oedem
if you suspect cor pulmonale.

Presentation to the examiner


On examination of the child;
-Always mention: whether the:"ct:Uld was in respiratory distress or not at ret
whether the child was cyanosed, whether the child was clubbed or n('
64 and the respiratory rate.
Mmtion only if present· dysmorphology. scars. mediastinal shift and lym·
phadenopathy.
T/Jt'n: describ~ your findings on palpation (TVF and expansion). percussion
and auscultation (breath sounds and .my additional sounds).
11\en say that these findings are consistent with whatever you think the
1llagnosis is.

65
Nephrology 4
Kenai questions are common in the examination. You should have a grasp of
lht basic physiology of renal function since some basic science knowledge is
t~ix:ed. The clinic'!!_ exa~~tion section is inCO!J?Q~at~g with the dintcal
etetiQD...of-th.~a~troenterq_l~eter (Chapter 6) since it is usu~ll~ exam-
11'\fd.as -pa.'rl.Qf the -~b_dominal examination.

f'he hmctions of the ki~y are as follows:


I Fl~nd electrolyte homeost~. '
J Excretionofw~I!C~~gs.
' Hormo nal: vitami~~etabolism (1-al~hydroxy~of
25-iWdroxvchQlesaici~ol), erythrO£oietin proauctiOn, renin p_roduction
and~la~~:Qduc tion.
4 Acid-base ho~
Rlnal blood flow acc.ounts for about_t26;)}Qt th! cardiac output. Most oUbjs
t•JProXlmately WQ) ~rried to the n,tnal s~~tfi"at ~, the ~ruli).
urwe ~g~n~ to be p_rq.du~d by. ~bout the third month 0~ g~tion. The fetus
6 not 5,e ly _!)n_ the kidney:; for ~was~e product excretion since this is
f'l'lormed by the placenta (it does, however, produce a _v ery dilute urine
which is a majo~mp_~ment of the a.tru}_iotic fluid). All the nephrons have
....n fo~ed bvQW.tl)_(cippr9ximately J,;inillion in_gach.kidney). there c:;an be
no further incr~_S.!!_in the number of the nephrons after bi_rl_h_(although
MmpenjiSto.r.y h~rtr.gphy is_pos~ible following daJ":Oege). Although the total
IIUmber d n~phron~ ~complete at birth the glomerular filtration rate
tGFR) at birth is only f2 ~gtin/1.73 m 2 (compared to adult values of about
'IIJDllmin/ 1.73 m:). Adult values are reached between the first and sec~!'c!
,..11 o.UUe.
In the cortex ultrafiltration occurs at the glomerulus and the filtrate enters
-.wman's capsule. Ultrafiltration is dependent upon renal blood flow, hydro-
IMUc pressure and plasma oncotic pressure (similar to Starling·s forces in the
llplllnry). The glomerular ultrafiltrate is then mostly reabsorbed (two-thirds)
ftum lht> proximal convoluted tubule tPCT). Sogium i~.eahs.ru:be.d..a~el~· 67
and is followed pass~elr. ~y wa!er. In addition gl~~e, potas~um (almost
complete absQ!RtiQnJ, oi_s~ri?<>Qate, ph<>§B.h.a te and amino acids ~ absorbed Ho .
in the ~- The straight portion of the 'PfT secretes some ot;gani.c acids such
asp~in. .
In the loop of Henle that R!_Otrudes into the medulla about 2q;,25.?1o-~f the
w~nd sodium is~& The fluid entering the l9$)p_is is~ut
le!!Y-e.s..h.)g>~lffitrt. There is a c~nter s:~rwt multiplie~ active
c hloride trans~ted from_!lle .t~ (wate_Limpermeable) ascendingnmb
of the loop of Henle. The result of this process is that the medullary inter·
stitium becomes very hypertonic and this is extremely important for uri·
nary concentration (remembering that the collecting ducts p·ass in very
dose_proximity to the tips of the loo~ Henle). The h~p_otoni(:Jiltrate
reaches the dis~~Qnvoluted tubull((teQII) whose walls are imperme~ble
to water. In its wa 1 tt\ere -is,Kowever, a ~~--J}u~t reabsQrbs a- sediq!ll
catioa in exchange for a p~~,ium or hy,Srpg~D i.on: it is controlled by
~~teroi}e:> Thus in the ~I sodium~chlom;b:....r~.qbSQri?,tif>n, pot~~l-'m
e xc-re_fiOn and ur.ipary acidifi~tigu occur. n tne last part of the j9Ul'ney
thr6'tgh the nephronthe urir.e pas~$ through the collecting ducts which
as mentioned before pas§ close tothe tiP.s.of the loops of Henle deep in the
medulla:_Tbe concentration of the urine is under the control of the hor·
monet(DH ( secreted from the posterior pituitary) which increases th;per.
meability of tlle collecting duc~_~d thus allows the con~n ol_~rin~
to occur. - -
The concentrating ability of the kidney increases during gestation: however,
the newborn term baby still _has a re~ilo/-. to c~rve s~ (com·
pared to older children). Other tubular functions are also_reduced, such as the
excretion of phosphate, which results in higher phosphate levels. A reduced
._bicarb~ threshold and ability- for hydrogen ion excretion means thai "Y
neonates may tolerate acidic insu lts less w ell. ..
Various hormones have an influence on kidney function. An increase in IIJI
plasma osmolality causes an increase in thirst and the release of ADH from f\1
the posterior pituitary gland (which as described above affects urinary con•
centration via collecting duct permeability). Reduced renal perfusion resullf
in the production of renin from renin substrl,\te (renin release is also controlled
by sympathetic stimulation). Renin is produced from the juxtaglomerular th
apparatus that is located on the afferent arteriole that enters the glome rulus. Ml
Renin release subsequently activates the conversion of angiotensinogen t(l dl
angiotensin I which is then converted by angiotensin converting enzyme ell
(ACE) to angiotensin ll. Angiotensin n increases thirst, produces marke~ ~~
vasoconstriction and increases the production of aldosterone from the zonn 1M
glomerulosa in the adrenal cortex. Aldosterone has its main action_on tht
OCT where it promotes the reabsorption of sodium and water (in exchang~
for potassium and hydrogen ions) thus completing the feedback loop by
·increasing the vascular extracellular volume. Atrial natriuretic peptide found
in atrial tissue (released in conditions of fluid overload) is a vasodilator and
promotes natriuresis. Prostaglandins are important in the distribution ol
blood flow within the kidney itself.
6s
tt11nal d·isease presents in a limited number of ways.
Plank mass
Haematuria z
PBin (loin pain, suprapubic pain, groin pain) Cl)
"C
Oedema .
Polyuria/oliguria ...0
:r
Hypertension 0
Metabolic consequences of renal disease such as rickets cc
A single umbilical artery in the umbilical cord is associated with renal '<
anomalies and the baby should have an ultrasound performed (and
possibly a karyotype).

Acute renal failure


.\ common clinical scenario is the child who presents with oliguria. Questions
will often present you with a few laboratory investigations and ask you to
•letennine the particular type of renal failure (that_is, prerenal, renal or post-
••nal). Know a ~.!_?J ca~ of each type of renal failure. Remember that it is
nl extreme importance ·to differentiate th~ types since raffi$1 correction of@-
''Dit failure diused by hypoperfusiQn will reduce the riskotpro~ to
~ ~o~te ~ar..n~s, and in tum to the m~e sen,Q_~~te c9rtical..nec~:.osis
whlch~ages g~Lpermanently. In p,S failure the kidn~ a~till
rmrEG.oniDg_to- ~~and w~(Uius urinary ~jum will be~).
The question may guid~ s~picion of acu~e~~ failure {l\.RF)1
I y desgibing a lethargic child who may be.,..de~ted or fluid ovexoJootled,
I~< Lg.mlfkgf-R.}, oe~atous, or with f~a~res of ac:Jc<:j~s (Kussmj!ul
l 11athing) or COIIJ..atose as a result of hyp~~ive encepnalopathy. You
huu~able tOdistinguish between prerenal and ren~L~ilure with appro-
1rlate la...~oratory inve?_tig~ti9ns-(see T'\ble 4.1).
In post-rena l failure the indice~_stre_e~~JY- variable and _!!L~ not useful:
~ou must therefo_~ place lmportan.c~ on y~r hi~ and examination. Unless
lht onse~as a~-th~ f!lay 'l:>e_a ~istory of redt!,ced urinary stream fqr some
tl~, a~in, ~~ passa~e of_renajy~~ or a history of a
ei!Mese·associated with renal.outflow.obstruction sucn as renal tubular acido-
... (which predis~ to ;'tones). toranank
Examine mass. .A"Patpable blad-
..., is associated Wiifu~obstruction.ln every patient with unexpla!Be<f
MU~re- an Ultrasound scan is vital t~excl_ude_opstruction.

Muauring GFR
Wtally a substance is required that is freelyjiltered by the glome(.Ulus but that
It neither rea~~ n~~t~~g. ~~~). Clinically creatinine clearance
II ur.ed as an ape~imatior:Lto~(cre~t.£"~_!D.in'"'Fnially reabsorbed
69
Table 4.1 Comparison of laboratory investigations in prerenal and renal f~ilure
Prerenal failure Renal failure
Urine osmolality (mOsmol/1) > 500 < 350 (inabi lity to
concentrate urine)
Urine sodium (mmol/1) < 10 (remember in >20
fluid depletion kidneys
-.~ Urine/plasma urea ratio
retain sodium and water)
>5 <5
Urine/pfasma osmolality > 1.3 < 1.3
'=
::J
U)
Fluid challenge ~ furosemide Diuresis No change
(frusemide) ·
<t Urinalysis Usually normal Haematuria, protein·
uria. wee. casts
E
cu Ultrasound scan Normal Normal. enlarged or
)(
increased echogeoicity
w

-
Oinic:al feat ures History rof ,.,rec:ipitant History of precipit ant
0
·;: e.g. severe gastroenteritis. e .g. haemolyt1~
."0~ Signs of fluid depletion.
Cold extremitie s:
uraemic syndrome .
May have fluid over-
G> Reduced capillary load with periorbital
cu retum, reduced skin and pedal oedema,
£l. turgor, sunke n eyes. hypertension, bound·
tachycardia. ·orthostatic. ing pulses. CCF. Visible
hypertension. neck veins.

in the ~). Plasma cre~e-.:.!one is not an i~al measu~11


~:Remember that ~e~on changes with body comj)ll
sition, age ~.ur-i-Rg~suffidency_~tinine is reabsorbed
v.;;yingttegrees. Neonatal crea_fii\ii\e'C
_i~ •t-ratieF~S--r.eflectnlafernal con co
trat~.H>~ however the~~na-tal-\<alues,.are--reacned in the first fc
days of lift:.
~
GFR = U x V /P (U =urine creatinine concentration (mg/dl); V = v olu11
of urine collected over period of time <.T~:- P = ~tinirt
(mg/dl)) ·
This must b e corrected for surface area by multiplying by 1.73/SA. Since c('l
lecting 2-l h urine specimens can be a difficult proces;; in children, GFR 1
sometimes measured by determining the rate-u&fall of concentration of~
injected radioactive isoto pe (e.g. Cr51 EQ.TA with radiation measurements ij

--
blood samples taken at 2 a,D9....4.-h post-injection). ·

Urea
The plasma urea concent! ation dep_ends on th ~CF.R and the~~cthJI
~- Its le~el may b~i!j.qe.ased ~:$h}gh.£rotein diet, cagE,<>Jic st~~h 1
~on, ~a and ~~ggry, st~W,~se, glomerular~~Y.P-O.tenslh
and rS]lal..2~-0lc.fu:e..d~sease. Its le\"el may be d~rea~ by a low p~dl
70 or high 1{;$: in hypen~s.n.amic-sta-tes. It is important to remember that II
I

\ "
l11rge reserve of renal funct_ion. means that the ~m~ and creat-inine
' ' cen.tr.atiops will not rise_until th~re is.ahout a~r uction in the GFR .
• l lnct' kidnt.'Y disei\::Oe has produc~d ,, rist;' in their C<mctc>ntrations it is more use-
lui to follow the progression of disease with plasma creatinine compared to
_ plasm<~ urea. z
CD
"0
Complement levels :r
Mtasuring complement levels is useful in various renal diseases. ~ed·
0
0
'(lmplement-l~re seen in lupus nephritis, p~~~ococcal g1_Q~J:\l.:: . CQ

~I.A~~ritis, me~ary-gfu~~lanephritis· (as~i·ated with<cJ~ '<


~or), c~mia , infective en~OQ!ditis and chronically
I cted atrioventrio,diit..Shrmts.

1
Urinary microscopy
Red cells imply haematuria. Know a list of causes starting from the top and
working your way down the urinary tract, dividing the causes into painful
and painless causes.
White cells are seen in any inflammatory infective disorder affecting the
urinary tract (more than 10 WCC/mm:t is considered abnormal).
Casts are cylindrical in shape and are moulded into the shape of the distal
renal tubule.
Hyaline casts are transparent and do not indicate renal disease on their
own.
Granular casts which look more 0'Ta n.ular...Qecau~_of_P-&ecjpit~tein
6'ifjFeir surfacu..t,e seen in g~r ~d n.:_bul~J;Lisease a lthough finely
g ranular castSmay be seen in normal children.
~ cell casts are typically seen in acu~BY~lo~pluitis and inte~al
nep§iti's: Thus if a child w.ith ~_fuund ~ have_~fell_ests, sus-
p{!Ct-acute..p,y..e.leR~tis.
Red cell casts are always patho logical and indicate renal disease -almost
always glomerulonephritis.
Provided that the urine has been collected in an aseptic fashion the demon-
• tration of bacteria after Gram stain indicates infection and is a useful indi-
cator until more confirmatory tests of culture are available.

...._. biochemistry
1'hete are a good source of questions for the data interpretation and grey cases
and you must therefore have a grasp of the co~moner patterns.

Acute renal failure


Tn tome extent this has alreaqy been dealt with but know the typical
bluc::he mistry picture. 71
• Sodium: high if volume depleted but low if fluid overload
• Potassium: raised
• Phosphate: raised
• Hydrogen ions: raised (low pH)
• Urea: raised
• Creatiitine: raised
• Urate: raised
• Calcium: low
• Bicarbonate: low.

Chronic renal failure


Here there is a slow and irreversible reduction in the number of functioninl
nephrons resulting in reduced glomerular and tubular function. This resul~
in a gradual onset of uraemia as a result of declining GFR. Urinary osmqlalit)
will eventually equal the osmolality of filtered plasma.
- Urea is raised and will also reflect the degree of hydration of the patienl
Creatinine clearance will ir:dicate the degree of ~1 dysfunction.
-Plasma sodium will generally reflect the degree of hydration of the·patienl
there is, however, overall sodium retention partly caused by renin relea~
- Potassium is raised.
-Phosphate is raised secondary to phosphate retention by the kidneys.
-Calcium: in chronic renal failure vitamin 0 metabolism is affected by lacl
of 1-alpha hydroxylation. Thus a lowering of plasma calcium levels result
in osteomalacia (lack of bone mineralisation) and a secondary hyper
parathyroidism which results in bone resorption' and thus osteoporosil
(loss of bone density). These effects along with phosphate retention con
tribute to the pictUre of renal osteodystrophy.
-Acidosis helps prevent the patient from tetany·as the hydrogen ions dis•
place plasma protein-bound calcium increasing the total amount of ionised
calcium in the blood.
-Urate is raised.
- For completeness erythropoietin production declines and results in a nor•
mochron.tc normocytic anaemia.

Renal tubular acidosis (RTA)


,r
This is a much hated topic for candidates revising for ~ examination but a
very common question! I will therefore give it a disproportionate amount ol
space compared to its clinical incidence. so that f cov~r all of the salient poinu
neces!>ary to answer any questions relating to it. A comparison of proximal
and di~tal renal tubular acidosis is found in Table -1.2.
- Normal1trmary ncid~ficntion: .Plasma acid-base homeostasis is achieved pre·
72 dominantly by the kidneys controlling the amount of bicarbonate in tht
Table 4.2 Comparison of proximal and distal renal tubular ~dosis ~
Oistal RTA Proximal RTA
(Type 1) (1}rpe 2)
Age at presentation Childhood or adolescence Infancy
Incidence Commoner Rarer zCD
Main pathology failure of distal tubular Failure of proldmal tubul~;tr "0
=r
Metabolic picture
. hydrogen ion excretion
Normal anion gap.
bicarbonate reabsorptiof\
Normal anion gap. a0
Hyperchloiaemic Hyperchloraemic metabo.lic tC
metabolic acidosis with acidosis with inappropri.'tely '<
Inappropriately high high urinary pH
urinary pH.
Urinary pH Urinary pH never below Urine pH can fall below ;.s
5.5-6.0
~cal presentation Classically with failure to Classically with growth t 9 iture
(In addition to thrive from infancy. and vomiting. Hypokala~mia
f ..tures of Hypokalaemia presents as presents as muscle weakhess,
pNCipftating/ muscle weakness, hyporeflexia.
U~tive disease) hyporeflelda, polyuria, polyuria. polydipsia. In
polydipsia, etc. Renal addition features
stones and nephrocalcinosis of Fanconi syndrome mz.y be
are common ct. proximal present (see below). No
RTA. Rickets secondary to nephrocalcinosis.
bone buffering the acidosis.
Hypokataemia ++ +
hatment · Aim to correct acidosis to Aim to correct acidosis t 0
allow normal growth and allow normal grow:th;
prevent nephrocalcinosis; potassium and bicarbonate
potassium and bicarbonate supplements.
supplements.. Beware of
correcting acidosis before
potassium supplementation
because of possible life-
threatening hypokalaemia.
llcarbonate Small doses ruch as l-3 large doses such as 1o
ftplacement mmollkg/day mmollkglday
Prognosis Variable Good

plasma. Usually 85% of frltered bicarbonate is reabsorbed in the (1roximal


convoluted tubule in exchange for hydrogen ion excretion (at norma{ plasma
bicarbonate concentrations). The remaining 15% of the filtered bicazixmate is
reabsorbed by the distal convoluted tubule, again in exchange for hydrogen
lon excretion. The secreted H• ions combine with the urine buffer.; ammonia
(NH:J and ~PO~· Renal tubular acidosis occurs when the ki<iheys are
unable to maintain a normal plasma bicarbonate concentration.

let.I renal tubular acidosis: Type 1 RTA


Pntf1ophysiologtJ= There is an inability of the distal nephron to secrete hyd~
Jl"n ions (resulting in failure to reabsorb the remaining 15% Of filtered
73
bicarbonate and also a failure to acidify ttie urine). Thus metabolic acidosll
occurs. Since there is no hydrogen ion excretion the sodium fails to.bo
r~absor~d (\·ia the :-..:a/K/H pump) .md as a result of the intra\"aSCulilt
depletion that ensues aldosteron~ release increases and promote•
potassium loss.
Causes include:
Idiopathic
- Familial
- Drugs, e.g. amphotericin toxicity
Inherited diseases: sickle cell disease, osteopetrosis
- Syste~c ciiseases: SjOgren disease, SLE, chronic active hepatitis
Diseases causing nephrocalcinosis: hyperparathyroidism,
hypercalciuria, vitamin D intoxication, medullary sponge kidney
lnt~rstitial renal disease: chronic pyelonephritis, obstructive nephropathy,

Proximal ,enal tubular acidosis: Type 2 RTA


- Pntlrqphysiology: There is reduced prox!mal tubular reabsorption of bicat•
bonate. The extra bicarbonate in the tubular fluid reaches the OCT and
here thc:c is some compensatory reabsorption of bicarbonate ions
Eventually this capacity is exceeded and bicarbonate spills into the urin~
and the p)asma bicarbonate falls until an equilibrium is reached between
the plasmcr and tubular fluid: th<H is, all the filtered ~icarbonate is reab
sorbed (this occurs when the plasma bicarbonate is usually between 15 and
20 mmol/1). Urine can be acidified since distal hydrogen ion excretion is
normal. In an attempt to hold on to hydrogen ions, potassium is lost in the
OCT in exchange for sodium ions at the Na/K/H pump. Proximal RTA can
occur in isolation but is usually part of a more global proximal renal tubu·
lar dysfunction called Fanconi syndrome (see later).
Causes include:
- Primary/idiopathic
As part of Fanconi syndrome
- Familial disease: cystinosis, Lowe syndrome, galactosaernia, Wilson dis-
ease, h ereditary fructose intolerance, tyrosinaemia
Drugs and toxins: heavy metal poisoning (lead, cadmium, mercury),
acetnzolamide (carbonic anhydrase inhibitor}, out of date tetracyclines
Others: renal transplantation, renal vein thrombosis and interstitial
neph)itis.
In order ·to distinguish between the two types of renal tubular acidosis firstly
demonstrate that the child has a normal anion gap metabolic acidosis (by per·
fo(lJling a serum urea and electrolytes and blood gases), and an inappropriately
high urinary pH (a pH > 6 in the presence of metabolic acidosis is always abnor·
mal). ="iext you must demonstrate if the child can acidify their urine by lowering
the urine pH to < 55. This can be achieved by using the ;\jH~Clloading test. I{
the urinary pH falls below 5.5 then the diagnosis is likely to be proximal RTA:
74 if the urinary p H s tays <;tbow 55 the diagnosis is likely to be dis tal RTA.
Normal urinary pH values vary during the day and are 1ffected by diet but
ll't! usually between 5 and 6 (with a range between 4.6 ana 8.0}.

Renal tubular acidosis: Type 4 RTA


type 4 RTA is caused by a reduced production or unresponsiveness to aldos- z
terone, leading to a metabolic acidosis with hyperkalaemia. Urine pH can fall (1)
'"C
below 5.5 during acidotic states. It occurs in a number of conditions: .,::r
•· Aldosterone deficiency: congenital adrenal hyperplasia, Addison disease, 0
tubulointerstitial disease (hyporeninaemia) 0
c.a
b. Aldosterone resistance: tubuloin~rstitial diS(:ase, drugs (spironolactone. '<
amiloride, triamterine)
c. Others: post-renal transplant, chronic pyelonephritis.
Whenever you are given biochemical data with a low plasma sodium and
high potassium level consider aldosterone deficiency /resistance.

Panconi syndrome
This is an inherited or acquired syndrome associated with a defect of proxi-
mal tubular function with characteristic impaired reabsorption of glucose.
~phate, generalised amino aciduria, bicarbcmate, potassium, sodium and
water loss.
Oinically it presents with failure to thrive, polyuria, polydipsia.
hypophosphataemic rickets, hypokalaemia (weakness, constipation) and
proximal RTA. Of course the features of the precipitating disease will also be
unong the clinical features.
The causes are similar to those de5cribed above causing proximal renal
1\lbular acidosis.

lartter syndrome
This is another common question that you should recognise. The pathophys-
lolqgy is not tully understood. There is a defect in chloride (and thus sodium)
rtabsorption in the ascending loop of Henle. There is juxtaglomerular appa-
ratus hyperplasia. Tnis results in raised renin levels and consequently raised
aldosterone levels. There is a normal blood pressure (and rio peripheral oedema)
despite raised renin and aldosterone levels (and reduced pressor response to
Infused angiotensin}. There is raised urinary excretion of prostaglandin E2.
lartter can be distinguished from other causes of hyperaldosteronism by the
absence of hypertension.
- Metabolic picture: There are de<:n:z.~"'\:1 sodiur.:1., potassium and chloride levels;
metabolic alkalosis; and increased urinary c.'"\~oride "xc.retion. NB· You must
have a list of other causes cf t:ypochloraemk ~ypok~laernic metabolic
alkalosis in your differential diagnosis. They include: .:liw>etic abuse and
extra renal causes of chloride Joss such as pyloric stenosis, persisting diar-
rhoea or vomiting. cystic fibrosis and chloridotrhoea.
- Clinically: Failure to thrive, polyuria, i)Olydipsia, muscle weakness, consti-
pation (last four secondary to hypokaiaemia}, salt craving and tetany (sec-
ondary to reduced ion..ised calcium concentration d ue to a lkalosis). 15
-Treatment: Potassium supplements, sodium supplements and diuretic.
such as spironolactone (an aldosterone antagonist) and amiloride (block
ing distal K s~.::retion). Prostaglandin synthesis inhibitors for examplc1
indometacin are also used. This will improve the majority of biochemicar
abnormalities to normal: however potassium depletion persists to SOml'
extent.

Renal hypertension
You may be given some data for a hypertensive ~d as follows.
Sodium: 143 mmol/1
Potassium: 2.8 mmol/1
Bicarbonate: 32 mmol/1
Urea: 2.6 mmol/1
Creatinine: 35 j.Unol/1.
As mentioned above the presence of a high sodium and low potassium pat·
tern should trigger thoughts of hyperaldosteronism. The converse is also true,
in other words a low sodium and high potassium should make you think ol
hypoaldosteronism: the metabolic alkalosis adds strength to the diagnosis.
Remember that in terms of hyperaldosterone hypertensive conditions
relating to the kidney, you have to distinguish between renal artery stenosis
(usually caused by fibromuscular dysplasia in the paediatric population) and
primary hyperaldosteronism (Conn syndrome) -see Table 4.3. In Conn syn•
drome a useful screening test is to check the plasma and ':lflnary electrolytes.
Plasma K is usually less than 3.5 mmol/1 and urinary excretion is usually in
excess of 30 mmol/day (provided the child has not received diuretics or had
a high salt intake). Both cases will of course give a hypokalaemic alkalosis.
In the case of primary hyperaldosteronism two-thirds are the resu~t of an
aldosterone-secreting adenoma and one-third of adrenal hyperplasia and
only rarely adrenal carcinoma. The increased blood pressure will inhibit renin
secretion. Interestingly in adrenal hyperplasia serum' aldosterone levels
increase on ambulation whereas they decrease on ambulation in the case of an
adenoma.
Using catheter studies it is possible to sample blood from various sites, and
in the case of rena' artery stenosis the blood renin level in the lower iV<= will
of course be lower than in the upper IVC. The actual side of the stenosis can be
determined t>y sampling the blood from both renal veins (renin levels will of
course be higher on the affected side). By similar methods adrenal vein sam-
pling will help determine the affected side in Conn syndrome. Sodium/potas-
sium urinary concentration ratios may also be helpful. Renal arteriography

"'ailie 4.3 A comparison of renal amry stenosis and primary hyperaldosteronism


Renal artery stenosis Primary hyperaldosteronism
Serum renin High Low
Serum·aldosterone High High
76
: lhy be used to identify the anatomy of a stenosis more clearly. Other methods
j 1rlude a renal Doppler ultrasound scan and a captopril renal scan.
You should also know the other renal c~u.c;es of hypertension such as
lhmnic rena l failure and renal tumours.
Any initial investigation in a child found t-o be hypertensive must include z
•rlnalysis, urine MC&S, serum U&Es and a renal ultrasound. Fur".her inves- ('I)

l.ntlons will of course be guided by the .results of these. "'C


=r
y1tinuria
2.0
I hit topic come::. up in various forms in the examination. You should know cc
'<
that it is caused by impaired renal and gastrointestinal transport of the diba-
1( amino acids cystine, ornithine, arginine and lysine (COAL}. It :S inherited
In an AR fashion. The only clinical effect of this is the production of cystine
tfnal stones (in about 3% of sufferers) because c f its low solubility. 1his can
"" on to produce repeated infections, haematuria, obstructive nephropathy
•nd ultimately renal failure. In data interpretation 'luestions the condition
1111y be recognised by the following:

Urinalysis: yellow /bro'Wn hexagonal crystals


Positive urine cyanide nitroprusside test: also positive in Fanconi syndrome,
homocystinuria, generalised amino aciduria and other rarer disorders.
I ht ctiagnosis can be confirmed by urine chromatography or electrophoresis.
Radiological studies may show stones which are typically t;!ilateral and
•••flhom·in appearance. Treatment consists of a high fluid intake, alkar.isation
1•1the urine with bicarbonate/citrate (keeping the urinary pH over 7.5). Stone
1lluolution can sometimes be achieved with captopril or D-penicillamine.

Urine colour
IUd urine: Haematuria, haemoglobinuria, myoglobinuria, beeturia, acute
Intermittent porphyria, urates especially in neonates (with concentrated
urine). Serratia marcescens can form a reddish pigment causing a nappy to
look re~.
Jlack u r:ine: This may be caused by alkaptonuria after urinary exposure to
11lr (cat.~sed by homogentisic acid excretion). It is a lso 5E'e.O in melanotic sar~
comas resulting from melanin excretion in the u:'.."'le.
Urine I hilt darkens on standing: The urine could con min either porphobilino-
pn or urobilinogen. These are colourless, but on standing exposed to the
llr are converted to porphobilin and urobilin respectively, both of which
are orange-brown.

lntt.st and. Clinistix


nowledge of these w ill be expected (see Chapter 10). Clinistix is a urine dip-
llrk test that is specific for glucose. Clinitest is a urin.: dipstick te ~ that 77
detects reducing sugars including glucose (e.g. lactose. fructose and galact~
-useful for galactosaemia), but not sucrose. Note the false positives seen wit~
ascorbic acid and homogt.>ntisic acid.
See above for urine microscopy description.

These can usually be seen on a plain abdominal X-ray Only pure uric acid.
xanthine and oxalate stones will appear radiolucent, the~ may however be
detected on ultrasound scan.
- Cnlcium-contailling stonl!s (85"1.,): Calcium oxalate. cakium p,hosphate.
mixed. Causes: idiopathic. primary hyperparathyroidism, renal tubular
acidosis, hyperoxaluria and the milk-alkali syndrome
-Triple stones (magnesium ammonium phosphate, 10%): Associated with
infection (especially Proteus infection). Their formation is favoured by
high urinary pH. ·
- Uric acid stones (5%): Increased uric acid excretion, for example tumour
lysis syndrome. Their formation is favoured by a low urinary pH.
- Cystint stones (1%}: Cystinuria. Their formation is favoured by low
. urinary pH.

lnves~igations

- '
24 h urinary calcium. phosphate, oxalate, uric acid and amino acid urine
collection. Urinary pH. Calcium:creatinine ratio (usually < 0.2). Urine 1
microscopy and crystal examination
-UrineMC&S
- Plasma electrolytes, uric acid and blood gas
- Renal imaging to exclude obstruction or reflux.
Hyperuricaemia may be seen in gout,. Lesch-Nyhan syndrome, myeloprolif-
erative disorders, tumour lysis syndrome, high purine diet, hyperparathy-
roidism, lead poisoning, Down syndrome, exercise, starvation, drugs (low
dose salicylates, thiazide diuretics) and alcohol ingestion ·

· RENAL. RADIOGRAPHY :\'·· :~ , , ... :.~ >~ ·. · · · ·· ,· .-;. · ·,:


There are many radiological methods of visualising the renal tract and they
are all potential slides, parts of data interpretation questions. grey cases or
topics for discussion in the clinical examination. 1

Plain abdominal X-rays


These can be used to look for calcification in the kidneys. Nephrocalcinosis
is characterised by the presence of pyramidal deposits of calcium found
within the kidney parenchyma itself. The causes include renal tubular
acidosis {distal mainly), hyperparathyroidism, sarcoidosis, hyperoxaluria,
idiopathic hypercalciuria and the milk-alkali syndr<lme. Other causes
78
t calcification m the renal tract are caktum-containing stones, calci-
11
lltd tumou r, TB, calcified hydatid cyst, calcified haemorrhage, infarct o r
\ ,;t
The renal shadow can usually be ~ on a plain abdominal X-ray and
ltnal size can thus be estimated. Note that the long axes of the kidneys are not
vtrtica l b ut oblique and parallel to the psoas muscle. The right kidney is usu- zCD
Ally lower than the left kidney (a result of liver displacement). 'tJ
...0
=r

llllravenous "":-ogr aphy (IVU) 0


ca
'<
Pollow ing intravenous administiation of dye, serial X-rays are taken of the
._w tract. Always compare the films with a control film taken with no dye.
I'll! kidney outline should alwa~ be smooth and if it is irregular you should
consider renal scarring. The dye IS first taken up by the kidney within 5 min
polt-injection. Renal outline and size can be identified as well as the presence
of space-occupying lesions. Following this so-called nephrogram, the kidney
pelves followed by the ureters and bladder are outlined, and you should look
fGr strictures and stones.
A common slide is of duplication of the renal collecting system. It is com -
IliOn (F > M) with 30% of cases being bilateral. Here the kidney has two
...-rers leaving it, one from the U?per pole and one from the lower. The ureter
f1Dm the upper pole is usually associated with obstruction and the ureter
r.mthe tower pole with vesicoureteric reflux.
A hotseshoe kidney (usually asymptomatic) shows loss of the nonnal long
Dis lie o f the kidneys. It can present as a midline mass.

Micturatin g cystourethrogram (MCUG)


In this im·estigation the bladder is filled (via a urinary catheter) with contrast
dye and the child is ~-rayed durin~ voidi.ng. The main indication for this
InVestigation is followmg UTis .n chtldren m order to exclude vesicoureteric
rtflux. Be familiar with the grading system for vesicoureteric reflux. A poste-
r&or urethral valve can be easily demonstrated with an MCUG. There is usu-
ally a markedly dilated p roximal urethra. In some slides an MCUG and NU
INV look surprisingly similar ~ut you should look for the dye-introducing
aatheter in an MCUG to help ycu distinguish them.

Wtrasound
Extremely useful in diagnosing renal masses, renal obstruction, renal size and
lll'lal cystic d isease.
s
j
Cl'san
•· l:seful for looking at the retrc::peritoneal space that is not easilv accessible
~ with other types of scanning. ·
79
DMSA. DTPA and MAGl scans
These scans are included in data interpretation questions. DMSA (dim
captosuccinic acid) is taken up and retamed by the tubular cells in the k
ney. The scan is a static scan. It is used to determine renal_sl\ape and si
and renal function. It picks up areas of functioning renal tissue and uptn
is proportional to function. It will thus show the shape and size of the .kr
neys and will pick up areas of kidney scarring. It has a higher sensitivi
(ij
> and specificity for detecting scars as compared to IVU. function is usua
·~ split fairly evenly between the two kidneys, approximately 45-55% upp
:::s limit of normal. It should be performed at least 6 weeks post UTI for acd
en rate results.
<( A DTPA (diethylene triamine pentacetic acid) scan is a -dynamic ~
E excreted by glomerular filtration following venous injection. A Tc99m MAq
C'CS scan (Tc-mercaptoacetyltriglycerine) is another type of dynamic scan and
)(
w excreted from the kidney by tubular secretion. MAG3 scans generally gl

-
0
•t:
~!
"0
CD
C'CS
better pictures of tl)e tract when there is impaired renal function compared
DTPA scans. following intravenous injection the patient is scanned for em!'
sions by the tracer and a time/ activity cprve is produced. Thus the functi
of the kidney, from tracer fUtration through to tracer excretion from U
collecting system, is assessed. We can thus assess renal blood flow, rei\
Q.
obstruction, bladder voiding. (including assessing vesicoureteric reflux) at
determine GfR furosemide {frusemide) is sometimes injected to help dist~
guish outflow obstruction from a dilated non-obstructed tract (which ml
appear obstructed because of tracer stasis). In the .case of a dilated · n<(
obstructed outflow tract, furosemide (frusemide) will help wash ·out the ~ I
tope from the kidneys, but in .the case of a truly obstructed tract there will b
no washout (see Fig. 4.1 ).

Understanding the DTPA scan tFig. 4.1) .


The letters (a), (b) and {c) cor:espond to the letters on the graph in fig. 4.1:
a. A normal kidney
b. An opstructed kidney
c. A kidney with hydronephroSis (non-obstructed).
1. In the normal kidney initially the count of tracer will increase
sharply from 0 as the DTPA,,is injected, followed by a slower rise~
the tracer is taken u.p by, the .kidneys. This reaches a peak at aroun{
3-4 min.
2. As DTPA begins to be excreted from the kidney we can see the counl
gradually fall as the tracer leaves the kidney and entt?rs the outflow
tract.
3. In the case of the obstructed kidney we can see that. DTPA is taken
up by the kidney but fails to be excreted, shown by the failure of
the tracer count falling. We can see that injection of furosemide
(frusemide) has no effect on curve (b) but results in excretion.·of
tracer in curve (c) simply implying that there is a true obstruction
rather than a dilated non-obstructt!d system in case (b) and the
·so converse in curve (c).
~
+
z
I
!.
CD
"0
J
0
~ 0
§ cc
'<
-~
0
~ (c)
'6
tl (a)

10 20 30 40 50
Time (minutes)

lilt. 4.1 A typical OTPA scan result from a normal and an obstructed kidney.

Hypertension
Hypertension is a common presentation of renal disease in the child popula-
tion. In se\.•ere cases the child may present with hypertensive encephalopathy.
There may be· a past history of abnormal urinalysis such as proteinuria or
a.ematuria. Plasma U &Es may fail to have been taken in response to these uri-
nary .results, and the .renal disease may have progressed until the child pres-
lnts in chronic :enal failure. Look for specific clues such as a family history of
hypertension, previous UTis or drug ingestion. Examination clues include
looking for syndromes, especially Cushing syndrome, William syndrome
(hypercalcaemia), neurofibromatosis (renal artery stenosis) and phaeochromo-
cytoma, listening for renal artery bruits, differential blood pressure in arms
and legs (coarctation of the aorta), signs of raised intracranial hypertension
(Cushing reflex), obesity, abdominal masses (e.g. nephroblastoma or
hydronephrosis) and virilisation (congenital adrenal hyperplasia). Retinal
hypertensive changes are indicative of chronicity of the hypertension. AS in
•dult hypertensive disease examination and investigations will be geared to
looking for cause and effects of the hypertension on various systeins.

Mlstory of skin rash


A common clinical scenario lS the child who presents in renal failure who has
had a history of a skin rash. The possibilities are: 81
+Q)

:E
1. Ht•1focll-Scllonlc>ill purpura: This is an allergic ,·asculitis (lgA mediat~
with the same pathological findings as IgA nephropathy). It may be prt
ceded by a \'iral or streptococcal illness. The M:F ratio is 2:1. peaking I
the winter months. It is usually first noticed as maculopapular urticaria
type lesions over extensor surfaces mainly of the legs and buttocks. I
::s addition there may be some diffuse cutaneous oedema on the face an~
C) dorsum of the hands a nd feet_. There is then a fairly rapid progression rJ
c; the lesion into the classi~ non-thrombocytopenic purpuric ·rash. At th t
> time of the skin lesions the child is ,usually welt This may be followe
·~ by abdominal pain which is classically colicky because of gastrointestl
::s nal im·ol\·ement causing oedema and haemorrhage into the gut wall (G
fJ)
c( haemorrhage may cause melaena, fresh rectal or occult bleeding). Th
.. vasculitis may act as an apex for intussusception. Abdominal symptonu
E
ca may precede the onset of the rash. Arthritis oc~rs most commonly i~
)( the ankles, knees and hips (referred hip pain ~y be re$ponsib.le fol
w abdominal pain). Renal involvement occurs in one-:.half to tWO-thirds of

-0
·;::
.~
"C
Q)
ca
cases, with microscopic haematuria occurring in about 50-7.0""... About 1
quarter of cases may dem onstrate varying severities of nephrotic syn
drome, nephritic ·syndrome arid may be responsible for end-stage rena~
disease in about toto·of all cases of HSP. There are no confirmatory tesU
0. for HSP. Treatment involves ob~rvation, analgesics and follow-up
Steroids may be useful in abdominal pain. The condition remits after
about a month with a good prognosis; however patients must be fol·
lowed up since in some of these patients there will be a progression ol
the renallesions•.Other conditions that can produce a vascu~tic rash,
nephritis, arthritis and abdominal pain includ..- the connective tissue dis·
eases such 'as .SLE, polyarteritis nodosa and Wegener granulomatosis
You should thus consider an .a~toantibody screen and furth~r addition·
al tests if-your diagnosis is uncertain.
2. Streptococcal disease: Post-streptococcal glomerulonephritis occurs 1-3
weeks following a group A streptococcal infection of the throat or skin. The
onset of nephritis is heralded by the onset of perior:bital oedema and a
smoky /tea/cola-coloured urine. Oliguria occurs and this is followed
by hypertension. Most cases are mild and often are not even noticed;
severe disease .can however occur and require dialysis. Nephrosis can
~lso occur but this is rare. Anti-DNAse B titres of antibodies are more
specific for streptococcal skin infections whereas antistreptolysin anti·
bodies are more specific for throat infections caused by StTqJtococcus.
C3 and C4 levels are reduced. Also reduced in SLE nephritis. mesan·
giocapillary glomerulonephritis, shunt nephritis and subacute bacterial
endocarditis (SBE).
3. Systnnic lupus erythematosus affection of Jhe kidney occurs in about SOo/o of
cases and severity vatje$· (rom very mild to very severe. Nephritis is the
commonest presentation of lupus in children. Proteinuria is common. Skin
lesions consist of the (lassie malar butterfly rash, maculopapular lesions,
alopecia, nail fold infarcts and telangiectasias. In lupus ~hritis there are
82 reduced C3 and C4 leve ls. ·
olytic uraemic syndrome
typical picture might include: Hb 7.1 g/ dl, wee 9.6, platelets 64; fibrin
adation products are increased; sodium - 146, potassium- 6.4, urea- 25,
tinine - 223. •
The classic triad that you should be looking for in the questions is of: zCD
) acute renal failure; (2) microangiopathic haemolytic anaemia (on a blood "'C
this is identified as schistocytes - red c:-ell fragments shred through the
::r
meshwork - which is Coombs' negative) and other features of 0
olytic ana€ .-.ia such as reticulocytosis or possible unconjugated hyper-
0
Ul
Wrubinaemia; (3) thrombocytopenia, which is variable. '<
Two main groups of disease are seen: (a) epidemic/typical (more common)
in younger c"lildren; (b) sporadic/epidemic - rarer and seen in older
hildren.
Jn the epidemic form the children tend to be younger and present with fea-
IU'tS of gastroenteritis (vomiting and diarrhoea, often bloody). The acute
I failure is usually of acute onset. The m ost co mmon causative organisms
the verotoxin from E. coli (serotype 0157:H7 strain), Salmonella, Shigella,
Clmpylobacter and Strep. pneumoniae. It is commoner in the summer months.
11\e sporadic type tends to have no such prodrome. It tends to affect older
dren. Renal damage is more severe but of more insidio us onset.
Other forms include hereditary and secondary ca uses, for example drugs
lek:Josporin), malignancy and post-renal transplant. These secondary causes
art howeyer commoner among adults.
A proposed mechanism is that an initial insult causes damage to the
lftlcrovasculature causing activation of prostaglandins and coagulation path-
ways leading to the development of microthrombi in the glomeruli.
HIJtologically there is a linear fibrin deposit in the glomerular capillaries. It is
peculated that there may be a deficiency of p rostacydin (a platelet inhibitor)
In the circulation (in the sporadic form).
Questions may make use of the large number of ·c omplications.

Ct~plications of haemolytic uraemic syndrome (HUS)


Gastrointestinal: abdominal pain, perforation and strictures
CNS: encephalitis-like ff!atures; persistent neurological sequelae may
occur
Cnrdiomscular: myocarditis, cardiomyopathy
Pancreatic involvement: IDDM, pancreatitis
Liver involvm~e11t: hepatitis
Eye: retinal haemorrhages Oc:cur in about a third of cases.
r..atment is consen·ative and symptomatic consisting of: transfusion of
t.lood and platelets; treatment of hypertension; careful fluid and electrolyte
btlence; treatment of renal failure with dialysis for severe electrolyte distur-
Nnce or fluid o verload; and antibiotics to treat a possible bacterial trigger. In
•ddition dipyridamole (an antiplatelet drug), heparin, prostacyclin infusions,
ltwr'Oids and other immunosuppressive agents have been used with varyir
euccess. 83
Prognosis appears to be better with the epi4il~mic
forms. The overall~
tality in the acute disease is about 5-10%. Th~ ~xtent and duration of re
involvement affect prognosis. The degree of CNS involvement is also
important determiner of prognosis. About 5% of cases may progress to
renal failure. .

-~ Hypochloraemic hypokalaemic metabolic a!kalosis


Several questions refer to the conditions that produce a metabolic alkal
·~ w ith low sodium, potassium and chloride. The list is as follows:
::::J
en - Pyloric stenosis or other conditions that result in significant gastric juic~
c( loss
- Chloridorrhoea
E - Cystic fibrosis
~ - Bartter syndrome
w - Use .of diuretics.
....!!!u
·;:::
The individual cause will be dictated by the clinical history and further inv
ligations, for example the sweat test for CF.
"C
G)
t1J
a. Cidosporin
Ciclosporin is commonly used in paediatric disease and you should be awar
· of its toxicity and side effects. It is nephrotoxic (sometimes causing difficullt
in differentiating from rejection in renal transplant children), results in hyper
tension, increases low density lipoprotein (LDL) and triglycerides, and rna I
result in tremor, gingival hypertrophy, hypertrichOSis, liVef enzyme dist\l I
bance ~nd immunosuppression.

Polycystic kidney disease


Questions occasionally come up on polycystic kidney disease. There are Ab
and Al forms, both of which may occur in infancy and adulthood. In th(
AR/i.ruantile type the baby typically presents with very enlarged kidne}'l
result:il\g from the presence of numerous cysts (dilated collecting ducts)
Renal bilure is usually present at birth and is of rapid onset. As a result of thl
reducthn in urinary flow, pulmonary hypoplasia is often present leading t(
respiraiOry .distress. Congenital hepatic fibrosis is also often present leadinJ
to hepaomegaly and impaired liver function and there may be bile duct ecta
sia (Caroli disease) leading to portal hypertension. Ultrasound shows a laC:
of differentiation between the renal medulla and cortex with the presence c
microqsts. Babies generally have a poor prognosis but some may be suitabl
for rerul transplant. Sodium replacement is important because of ongoin
sodium leakage.
Alth~ugh commoner in adulthood, the AD type may also occur in the pal
diatric ><>pulation. Children present in a similar fashion to adults with a
abdomhal mass, hypertension and progressive renal failure. There is cyst:
·84 d ilatation of the nep hrons which gradually enlarge, compressing a djacet
paren..;hyma and causing yarenchymal ischaemia. About 30% have
~ cys:.:s (iess commonly seE'n in the pancreas, lungs and spleen}, and
01neu:ysms are present in about 15% (about 15% of these di~ from the
It ng s-ubarachnoid haemorrhag<=). Treatment involves managinli!; •ht"
rtension, renal failu re and consid ering renal transplant.

male child who has a history of renal outflo w tract obstruction should
1 posterior urethral valves exclud ed as a possible cause. The age of pres-
lion in the questions may. vary from birth to 4-5 years of age de~nding
the severity of the obstruction caused by the valves. Indeed the '>'a!v~ may
1 caused urinary obstruction to such a degree as to have caused dysplas tic
rwys and p ulmonary hypoplasia a t birth. In the more severe cci::.es that
t earlier there will usually be a bilateral hydronephrosis presentmg as
ltral flank masses and renal failure of varying degrees. Older children
yptesen t to paediatricians because of parental concern about poor urinary
1m, urina ry tract infections or abdominal pain. An MCUG provides the
is by finding a dilated urethra proximal to the valves. The bladder
II is thickened as a result of secondary bladder wall hypertrophy.
tntmber that between 50 and 60% of cases are associated with vesi-
ureteric reflux. Treatment involves relief of obstruction (e.g. with vesicostomy)
ttlally followed by ablation of the valves ± trea tment o f the reflux.

entbined renal and neurological signs


Itt combination of renal signs and neurological signs is a pattern with which
"" should be familiar.
Wilson disease: Proximal renal tubular acidosis, Fanconi syndrome. Basal gan-
jia features and peripheral neuropathy may be seen (see Chapters 5 and 6).
IWttallrypertension: Any cause of acute or chronic renal failure resulting in
hypertension may result in neurological features as well as seizures and
hypertensive encephalopathy.
•PUll biochemical disturbance: By alteration of the normal biochemistry and
In particular plasma sodium concentration, seizures may be precipitated.
Haemolytic uraemic syndrome (see above).
A/port syndrome: This causes a glomerulonephritis (with thickened split
basement membrane), sensorineural deafness especially in the high
frequency range (may appear in later childhood) and ocular changes.
Microscopic haematuria is common and males are more often affected than
females. They may have recurrent macroscopic haematuria and onset of
renal failure in the early' twenties.
AD polycystic kidr1ey disease and the association with berry aneurysms (see
above).
Sick/" c.:>/ I disease can cause acute papillary necrosis and neurological features. 85
-Lend poisoning: Fanconi syndrome and signs of raised intracranial press
- Slumt nq7hritis: The association of a ventri~loperitoneai shunt with nep

Q)
- Tuberous sclerosis: Angiomyolipoma (often misdiagnosed as polycystic
"0 ney disea~ in the absence of other features of the syndrome) may lea
:::s hypertension and renal insufficiency. CNS features are a result of the p
C) ence of intracranial tubers (see Chapter 5). \11
CG
> - Dntg ingestio11 must never be excluded from the differential diagnosis.
·~
:::s Haematuria
(/)
<t Be familiar with a list of the causes, investigations and management
haematuria and proteinuria, available in most paediatric textbooks.
E Haematuria is a common clinical condition in paediatrics. The causes can
~ divided up as either painful or painless. The causes include: UTI, pyelonep
w tis, stones, hydronephrosis, trauma, bleeding diathesis, sickle cell dise

-
0
·c
.!
"0
Q)
CG
strenuous exercise, vascular malformations (e.g. hereditary telangiectasia)
tumours (e.g. Wum tumour). Glomerular causes of blood loss indude vase
tis (e.g. Henoch-Schonlein purpura}, any cause of glomerulonephritis, be
familial haematuria, Alport syndrome, connective tissue diseases, for exam
c. SLE, Berger disease (associated with viral illnesses) and SBE.
In the history one should determine the presence, site and nature of
pain, history of trauma, recent upper respiratory tract infections (includ
sore throats) or skin rashes (especially streptococcal-like skin rashes) a ~
recent medications causing a possible intE;rstitial nephritis (e.g. penicilli!\. 1
You should ask about a family hist~ry of haematu?a, renal stones or sf 1
sorineural deafness (Alport syndrome). You should examine for oede~
hypertension and renal masses (such as hydronephrosis} and l09k for ras
Investigations for haematuria should include: MC&S of the urine, F
U&Es, ASOT, antinuclear factor (ANF), C3, C4, C~. In painful haemat\l
include calcium, phosphate and urate levels. Send urine for Ca/Cr ratio, a
24 h collection for calcium, urate and phosphate. Abdominal X-ray, re
ultrasound (preferable) and possibly renal biopsy.
- IgA nephropathy (Berger disease) is the commonest glomeruionephritis
children. Males are affected twice as commonly as females. Gross haen1
turia (and more rarely microscopic haematuria) occurs shortly after
upper respiratory tract infection (or during) d. post-streptococcal d~t
where haematuria occurs generally 10-14 days after infection. There Jl\1
be associated loin pain. It is self-limiting.. Between 10 and 30"k of childlt
will go on to develop renal failure. Renal biopsy (rarely required) sho l
features identical to those of Henoch-Schonlein purpura. ·
- Benign ftmriiial lrnematurio occurs in children with persistent microsco1
haematuria usually without proteinuria: It is a. benign cond.ition with !
deterioro1tion of renal function over time. It tends to run in families soy
should test other family members' urine. Def.anitive diagnosis invol
renal biopsy where a reduced thickness of the glomerular basement mall
86 brane may be found.
jllfllllt ltypercnfcwna describes the cond1hon where cak1um excre·
/day exceeds > 4 mg/kg. It can be found in approximately 2% of chil-
. lt produces macroscopic ur microscopic haematuria which is usually
lnless. However the development \)t .:aloum-contammg stones (a
111\tial complication) will be associated with pain A random urine sam-
may be tested for the Ca/Cr ratio which in normal individuals is< 0.2
0.2, then perform a 24 h urinarv collection to determine daily calcium
rttion. Treatment 1s conservahn• wtth a reduced salt and ca!ciu.m diet
ut to the extent that growth ~ affected), h1gh t1utd mtake and occasion·
lly the use of thiazide diuretics that reduce renal calcium excrehon

11\Ay be caused by excessivE' drinking (e.g. psychogemc polydipsia).


caemia - diabetes mellitu.<O, diabetes insipidus (central or nephro-
) • Fanconi syndrome, follo1h'ing prolonged obstruction to the urinary
chronic renal failure and dO"\ cause of hypokalaemia that induces a
JNI)gei:U"·c diabetes insipidus.

and the kidney


a list ot the commoner drugs that are assooated with nephrotoxtcitv
Mlmbranous GN: gold, penicillamine. captopnl
'"lfrstitial f!ephritis: penicillin, cephalosporin, NSAIDs
lllurl tubular damage: amphotendn. heavy metals (gold and mercury).
qtotoxics and aminoglycosides

lllhroblastoma
1 pattern of an abdominal mass, haematuria as well as hypertens10n m a
lid aged between about 1 and 4 years should suggest the diagnosis ot
~lastoma (Wum tumour). It is derived from mesonephric mesodermal
Ut. M > F. Jt is inherited in about one-fifth of cases with the remainder
llf\1 sporadic. It is bilateral in 5-10% of cases (more common in familial
. .). It presents as a smooth unilateral mass in the flank which may enlarge
1pidly. Pain may be present. Hypertension occurs due to pressure on the
N l artery causing renin production. Microscopic haematuria (in a third of
Mltnts) is usually seen as opposed to gross haematuria. Generalised features
11h as fever, weight loss and anorexia may be seen Do not forget the rare
~~~entation of heart failure in Wilm tumour as a result of proximal spread of
II tumour through the renal vein and IVC into the heart which can cause tri·
lipid regurgitation. Blockage of the IVC can cause distended veins over the
lin of the abdomen. Pulmonary metastases are present m about 10% of cases
diagnosis (often seen as cannon ball metastases)
It spreads by direct extension. blood spread and via the lymphatics.
lttastases are found m about 15°'" at presentation <mostly cannon ball metas·
Ill in the lungs). Investigations mclude mtravenous pyelogram, CT scan
\d biopsy. The IVP shows characteristic distortion of the calyceal system or
tllecting system with however no change m the d)w; of the kidnev 87
Know the associations:
- G~strointestinal abnormalities
- Bed<:wjth-Wiedemann syndrome
,(J> - H~mihypertrophy
- Aniridia in association with 11 p 1~ deletion
:::J
C) --Genitourinary abnormalities such as adreual hypoplasia and horseshoe
:kidney
C'CI
> - Neurofibromatosis.
I
·~ Treatment consists of radical ·nephrectomy ±radiotherapy and chemotherap
:::J . . I
C/)
<( Neuroblastoma

E The other common intra-abdominal tUmour of infancy is neuroblastorn


C'CI It occurs most commonly before the age of 2~ years (one-quarter before 1 year
><
w It is associated with Beckwith-Wiedemann syndrome, nesidioblastosis an

-0
'i:

,.!!!
(J>
C'CI
neurofibromatosis. It may occur anywhere along the sympathetic nervous sy
tern, most commonly in the aci renal gland but is also seen in the rr 'di:1stinu
(posterior thorax with thoracic cord invasion), neck and pelv~.lt prese!).ts ~i
an irregular mass arising from the f,lank and unlike Wilm tumour it c rosses
midline. It often presents late when metastases are present (in·about 70%
a.
cases). Metastases are most commonly found in bone, bone marrow, lympha
1
ics, liver and subcutaneous tissues. Thoracic involvement may cause a.Horn
. syndrome or tracheal or vascular compression. Heterochromia iridis may ~
present. Skin involvement, common in infants, may cause raised bluish no
tender nodules. Be .1y metastases produce bone pain, proptosis and '.r acc<>¢11
eyes' (periorbital bruising caused by invasion of the sphenoid bone or perio I
bital tissues). Tho:' bone marrow may. be invaded in about 50% of cases. In ch\1
dren less than 1 yP.ar of age a syndrome consisting of an undetectable prima
tumour, most often in the ~d.rena! gland, with metastases to skin, bone marro
and liver (howev er not involving the bone) may be seen. 1hi.s form of neurol
lastoma often Undergoes a spontaneous remission without t;reatment. It is se I
in about one-tenth of all cases. The opsoclonus-polyclonus syndrome consis
of acute cerebellar a.."'ld truncal ataxia with .'rapid dancing' eye movemen I
Occasionally chronic watery diarrhoea may be seen (Vemer-Morris
syndrome) due to vasoactive intestinal peptide (VIP) Secretion. Olfactory ne1
roblastomas may ca~· recurrent nose bleeds and obstruction. The investig
tion involves IVP, Cf scan and biopsy. The IVP demonstrates the classic
'drooping lily sign' as the kidney is pushed down and laterally by the tumotl
Unlike Wilin tumour, the calyceal architecture is maintained. On a plain AX
calcification may be seen in about half of all cases. Increased levels
catecholamines are found and in some cases also ~ised HMA and CMA.

Congenital nephrotic.syndrome
There are two types:
' .
-Finnish type (the more common form): There is a raised maternal senJ
88 and amniotic fluid antenatal AFP, large placenta (usually more than 25%1
infections such as Pne11mococws and Hnemophilus.injluen::Ae. Pneum\> 1
sepsis is a particularly important problem and vaccination
PneumO\'aX shoulJ be offered. Peritonitis can occur because o (
Pneumococcus ot Gram-negative organisms.
b. There is an acquired thrombophilia because of the loss of dotting Jl\1:11•
such as antithrombin fu in the urine. Thrombosis can occur in tlw r•1rll
vein, pulmonary and peripheral vasculature.
c. Plasma protein loss may, result in rickets secondary to urinary loss Ill vi~
min 0 bi:flding globulin. Hypothyroidism may occur secondary to thy 11
binding globulin loss.
It is beyond the scope of this book to go into treatment options but th •.,
readily available in most paediatric texts. General measur~ ,i nclude: ( J
restriction; (b) if fluid depleted, the use of albumin i.v. or if fluid overhlfl•
then diuretics are given; (c) steroids or immunosuppressives; (d) propl ~ ~~~~
penicillin.

Hepatorenal syndrome
Renal failure (marked by the onset of oliguria - distinguish from
failure secondary to dehydration) may develop in·a child with sevor
disease and is called the hepatorenal syndrome. There is reduced
p~rfusion as a result of the accumulation of vasoactive substances
thought to be usually d~ared .by the functioning.liver. .The 1,1rinary fl
excretion is low with a normal tubular function. Improvement in renttl
ure will only occur if the liver failure improves drastically; the
ot.~erwise is poor.

atenal vein thrombosis (RVT)


It is essential that you are familiar with the clinical prE:Sentation of RV I
occur in a state of severe dehydiation (such as a newbom baby who ~
and not having sufficient fluid intake) or a hypercoagulable state
nephrotic syndrome, in polycythaemia or protein C deficiency).
there may be renal enlargement, flank pain, irri~bility (in a baby),
(microscopic or macroscopic) and declining renal function. Renal
will help make the diagnosis. Beware the proS!e5SiOJ;l to h ..,..,.t·hl•~"~wltl
respiratory distress indicating the possibility of a secondary
embolus. Treatment 'is }'litfi hydration,and anticoagulation.
''

Prune belly syndrome


This com,-: up in the slidt, so be (amiliar with a picture of it. In
you ma; .;~ asked further questions relating to it. !\iinety-seven 1
occurs in males. There is: (1) absent anterior wall mu!!(:Ulature; •(
tourinary abnormalities: . bilat~ral cryptvrchidism, non-obstructiv•
·90 tion of the renal tr.a.;:.t \the ureters are often tortuously dilated), vesiC!t\1
tllux (in 75%) and cystic renal dysplasia which may lead to chronic renal
llure. Antenatal oligohydramnios may lead to varying degrees of pul-
11\llry hypoplasia. Recurrent urinary tract infections are common as a
ult of stasis; (3) cardiac abnormalities; (4) musculoskeletal abnormalities.
ltrognosis is related to the severity of renal involvement. z
CD
"0
::r
a
0
cc
'<

91
eurology
5
urology has a significant presence in all the sections of the Part 2 examination,
neurological cases are especially good at discriminating clinical proficien-
•nd confidence. In paediatrics, where neurological signs and symptoms
•V result from a diversity of causes, they also test the candidates' wider
IIIWiedge.

hll would be a good basic science topic since many disease states ca use a
lltruption of normal function and this in tum leads'to disorders with w hich
11 should be familiar. ·
Cerebrospinal fluid is continually produced as an ultrafiltrate of plasma
•m the choroid plexuses in both lateral ventricles. The CSF from the right
ulleft lateral ventricles then flows into the third ventricle through the fora-
' n of Monro and then into the fourth ventricle via the aqueduct of Sylvius.
Ihe CSF then passes through a central foramen of Magendie and two lateral
remina of Luschka into the subarachnoid space to sur round the brain and
tlnal cord. It is then absorbed mainly by the arachnoid granulations that
1r jt!ct into the dural venous sinuses. The normal opening pressure of the CSF
'I 18 em H 20 and at any one time in an older child there will be between 80
1\d 150 ml fluid .

Nl&lfrocephalus
'fou should be familiar with the causes of hydrocephalus - defined as an
Increased amount of CSF, usually under increased pressure and usually with
eorne degree of dilatation of the ventricular sy.stem.
In paediatrics it is useful to classify the types as follows.
Obstructive
Decreased absorption of CSF
t Increased production of CSF.
Alternatively a different classification of communicating and non-communi-
Atlng hydrocephalus exists. Corrununicating 'implies that CSF can flow
93
through the fourth ventricular foramina into the subarachnoid space but Cl
not be absorbed by the arachnoid granulations. Non-communicatl
implies that there is little or no communication between the ventricles al\
subarachnoid space.

Aetiological factors
- Obstruction to CSF flow: This can occur at the level of the foramen of Mon
third ventricle, aqueduct of Sylvius, and foramina of LUschka and Magend
of 'tfie· fourth ventricle. Any of these obstructions can be caused by:
1. tumours
2. congenital abnormalities, such as the following:
- Dandy-Walker cyst: This describes the absence or deficiency of the
cerebellar vermis and fourth ventricle· foramina outlets together
with subsequent cystic dilatation of the fourth ventricle leading to
hydrocephalus (in 80% of cases), and can sometimes be seen with
posterior fossa transillumination.
Amold-Chiari malformation: This describes a small posterior fossa
and downward dispiacement of the cerebellar tonsils and medulla
into the foramen magnum often associated with spina bifida.
Aqueduct ste11osis (which may be X-linked or sporadic): In the rarer
X-linked form the thumb is commonly flexed in opposition and thl
first metacarpal is short. A possible slide of a child with a large
head and overlapping fingers should alert you to the possibility of
X-linked hydrocephalus. Sporadic cases of aqueduct stenosis ·
account for the vast majority.
Aneurysm of tfte t>ein of Galen (causing obstruction at the level of th~
aqueduct).
Aclzondroplasia where bony abnormalities result in obstruction.
- Decreased absorption: (a) Infection: ~eningitis or encephalitis includil1j
intrauterine infections with toxoplasmosis, CMV; (b) intraventricular IJ
intracranial bleedsi (c) sagittal sinus thrombosis with resulting increa5C11
pressure and reduced CSF absorption; (d) arachnoid villi hypoplasia.
-Overproduction of CSF: Rare and usually caused by a choroid plexw
papilloma.

Many questions in the exam will ask you to discuss the causes of abnormftl
CSF results. In order to do this you will need to know the normal values (S(i
Table 5.1). Table 5.2 describes the expected findings with different types ol
meningitides that you are likely to encounter in the examination.

Additional important notes on CSF values


- Remember that if you are given CSF values with the presence of erythrocytelt
and white cells and you want to determine whether their presence is caused
94 . by a bloody tap or intraventricular haemorrhage, or CSF inflammation, thc11
5.1 Normal CSF values for different age groups

~pptarance
Wlllte cellsl~-tl
Ptfrmorphs/111
Premature
Clear
(}-100
0
Neonate
Clear
o-ts
0
Infant
Clear
(}-10
0
Child
Clear
o-s
0
+
zCD
Lwmphocytes/111 (}-100 (}-15 (}-10 o-s c:
·~ cells/111
IIIII o-'1000 o-soo 0 0
n .lng/1 1~ 0.3-2 0.2-1 0.2-0.4 ""0
Qkose mmol/1 213 of blood 0
Ul
glucose in all cases '<
HI A neonatal lumbar puncture is more likely to be traumatic with more erythrocyt~ on
lllil'ostopy and does not necessarily Indicate intraventricular haemorrhage (IVH). Neonatal
e Wmay be incorrectly reported as xanthochromic if then~· is coexi$ting jaundice.

.a
flltle 5.2 Abnonnal CSF findings tound with different types of meningitis
Bacterial Partially treated Viral TB
meningitis meningitis meningitis meningitis
'• ranee Often turbid Often dear Usually clear Not d ear.
~I Fibrin wee
occasionally
N seen

ll ".!!lmorphs/111 Up to so ooo Up to 1000 Few Up to 1000


lf'nphocytes Few Up to 1000 (i.e. Up t o 1000 Up to 1000
mixed picture or (i.e. lymphocytes
It "'' with lymphocyte predominate)
predominance)
MC&s Organisms Often sterile No organisms ZN stain for
often seen culture seen or grown acid-fast
bacilli
C!'•in g/1 1-5 1-2 < 1.5 1~

llucose < 213 blood Normal or tow ApproJC:i mately Very low
same as plasma
(except mumps
and herpes
simplex. see below)

calculate the ratio of white:red cells. In peripheral blood the ratio is 1:500.
Thus a relative excess of white cells in this ratio implies that there is some
meningeal inflammation present.
A cerebral abscess can give a sterile tap but there is sometimes a raised protein
count and a lymphocytosis.
Don't forget leukaemia in your differential diagnosis of a CSF lymphocy-
lotls. Check the blood film! (CSF glucose is usually less than two-thirds
ltlood glucose.)
In herpes simplex encephalitis there is a haemorrhagic encephalitis and
the eSF is often bloodstained (increased erythrocytes). The wee is 95
increased as is the protein count and the glucose may be low in 20%
cases. Remember that clinical features may include strange behavi
(e.g. lip smacking) because of invoh•ement of the temporal and front
lobes.
-Mumps meningitis is an exception to the viral meningitides and CSF gl
cose is often low.
-"'
.~
-Occasionally TB meningitis caa be confused with a cerebral abscess
looking at the clinical history and CSF values alone, since both have a 1
~ ' indolent history of several weeks of fevei,-·headache and other non-spec!
::l
CJ) . symptoms~ Both also give a ra·ised CSF protein. count and sterile cultu
TB meningitis however gives a low CSF glueose.
<t..
-The causes of a CSF with a raised protein CO\U\t include: Guillain-BaJ
E syndrome; spinal block; TB, fungal. bacterial and viral meningitis; cerebt
"'
><
w abscess; neurosyphilis; subdural haematoma; cerebral malignancy a

-(J acoustic neuroma.


't:
-The presence of oligoclonal bands in the CSF may be caused ~ y sarcoid
.!! sis, multiple sclerosis, SLE, SSPE, subarachn01id haemorrhage (also I
'0
Q) glucose) and neurosyphilis.
"'
a.
CSF microbiology
The commonest orgacisms causing meningitis in the neonatal period reA•
maternal vagirull ·oolonisation. ·
-Group B Streptococcus
-E. coli
- Listeria -monocytogenes.
After the neonatal period:
- Staphylococcus aureus
- Staphylococcus epili;ennidis (especially if there are indwelling prosth
such as shunts)
- Haemophilus influenz.ae type B
- Neisseria meningitidis
-Streptococcus pneumoniae (sicklers at increased riisk)
- Pseudomonas
-:-.Klebsiella
-Tubercul~
- Salmonella (sicklers at increased risk).
Neurological sequelae following meningitis are rmost common in pneut"
coccal meningitis, less common in meningoc~occal and least comn
(but still a significant problem) in Haemophillus influenue meninQII
However you should remember that the eff~ of reducing subseqlll
neurological sequelae with dexamethasone is jgreatest with Hllemoplil
meningitis.
96
general all cocci are Gram positive except Neisseria. All bacilli tend to be
negative except the bacilli Clostridia. Corynebacterium. Lactobacillus and
rln.

z
Cl)
comes up in the data interpretation questions and you should be famil- c:
lth the commoner patterns: it can be a complicated topic but you are only 0
ted to recognise the commoner patterns. It is usual in the questions that 0
(Q
will be given a montage or map of where the leads are attached to the '<
lp. The traces from the odd number leads are usually from the left side of
htad and the even number traces from the right side.
llornetimes a scale/amplitude or time marker is included as well.

lc rules of int~rpretation
Make yourself familiar with what a normal EEG should look like (see
"'' 5.1).
Look at all the traces from the EEG. Now determine whether the EEG is
normal or abnormal.

1,, The normal EEG.


97
A spike wave

A slow wave
Fig. 5.2 Spike and slow waves.

1 second
Fig. 5.3 Petit mal epilepsy.

3. Ihen find out whether this abnormality is generalised: that is, occurring
m all the traces, or limited to particular traces (localised to a particular
part of the brain).
4. Determine 'tbe -nature of the wave .abnormalities- spike waves or '$lGw
waves (see Fig. 5.2).
5. Now look at the amplitude of the EEG waves (high or low voltage).

Petit mal epilepsy (Fig. 5.3)


The EEG shows typical three spike-wave complex cycles per second (3 H t
The changes are synchronous in all the leads, and may be accompanied by 3
absence attack which may be precipitated by hyperventilation (family histo~
in 20%).

Hypsarrhythmia (Fig. 5.4)


(This is an EEG description and not a clinical diagnosis.) Here we can ~
chaotic pattern of high voltage slow waves and multifocal spike waves wit
no constant pattern associated with infantile spasms (in about 50% of ~
cases). The slow waves and spike activity disappear with the onset of a
infantile spasm. Hypsarrhythmia is enhanced by sleep and drowsiness. Per

1 second
98 fig. 5.4 Hypsarrhythmia.
nr onset is 3-12 months. Strongly associated with mental retardation,
ytd motor development and loss of acquired skills. Know a list of causes
urantilc sp"asms:
10% idiopathic
l'rrnatal: tuberous sclerosis (25%), congenital. infection z
CD
l'frinatal: birth asphyxia c
l'oltnntal: meningitis, encephalitis, head injury, severe hypoglycaemia, a
I'KU and other aminoacidopathies. 0
CQ
•propriate investigations will include examination of the skin under '<
lOCI's light for ash-leaf macules, skull X-ray for calcification (see later), CT
•n (for calcification, atrophy and congen~tal anomalies such as agenesis of
corpus callosum). An abnormal CT scan is associated with a poorer prog-
lt. Various serological and metabolic screens might also be indicated.
l'rfatmmt of infantile spasms: ACTii/prednisolone/vigabatrin. Be familiar
with the classic infantile spasm (often described as the opening and
d05ing of a book repetitively). Mothers may occasionally misinterpret the
child bringing their legs up to the abdomen repetitively as colic or
(01\Stipation. Fifty per cent will go on to develop other types of seizure,
• peciallyf?f the grand mal type. ·

ubacute sclerosing panencephalitis {SSPE) (Fig. 5.5)


1111 we.see an EEG with relatively normal EEG activity punctuated by ~ur­
nl paroxysmal bursts of high voltage slow waves occurring at regular inter-
•11 (periodic complexes). These occur synchronously in.all the leads. These
ftodic complexes may be associated with myoclonic jerks. Diagnosis is con-
lmtd by fmding high anti-measles antibody titre in the serum and CSF.

tlt~pe5 simplex encephalitis .


1 Jn the previous example. here we see the presence of periodic complexes.
lfftPOrtantly, howe..-er, they do not occur in all the leads but only in those over
.... wmporal lobe. This is highly suggestive of-herpes simplex encephalitis.
ldttr confirmatory tests are described later. If one suspects herpes simplex
._,halitis one should perform a lumbar puncture, viral titres (especially,
ltttpttic + PCR), restrict fluid to nyo-thirds maintenance, start i. v. adclovir
•IIIII CQnsider steroids and anticonvulsants. Periodic complexes are also seen
Ill Creutzfeldt-Jakob disease.

1 second
Me- I.S Subacute sclero~ing panencephalitis.
-> 1 second
"'
·~
Fig. 5.6 Grand mal epilepsy.
:::J
C/)
<(

E
"'
><
w

-CJ
'i:
.!!!
"0
Q)
C'O 1 second
Q. Fig. 5.7 Myoclonic epilepsy.

Gr.and mal epilepsy (Fig. 5.6) _ .


Patients with grand mal epilepsy may have normal intetidal EEGs. Dutirlg ~~
a ttack there will be spike waveS and polyspikes fllat usually occur at the:Stal
of the episode. These -are bilateral, synchronous in all leads .and .geneull
symmetrical over both hemispher-eS.

Myoclonic epilepsy (Fig. 5.7)


Myoclonic epilepsy is associa~ with synchronous periodic polyspik
(at about 3Hz) with a normal interictal EEG. It ·accounts for about 10%
childhood epil~psy. Attacks, which usually begin around puberty, can be pr
cipitated by sleep deprivation or akohol. Attacks may consist of a sudd~
jerking of limbs usually symmetrically and bilaterally often affecting tl
arms. They may proceed to gene~alised fits. Fits are usually in the m ornb1
within a few.. hours of waking. A sleep-deprived EEG is useful in making lh•
diagnosis. Treatment is with sodium valproate.

Other patterns
- Focal abnormalities can often be detected with .the aid of EEGs. Theru ~
usually high amplitude slow wave activity seen over space-occupyh't
18ions. Also seen after substantial vasculcfl1esions or advanced neurodt
generative diseases. Not uncommonly the focal abnormality may becoo
generalised.
-Onset of epileptic EEG activity with a photic stimulus is diagnostic I~
'100 photosensitive epilepsy. It usuaUy t enu"'ts in adult life.
ISenign Rolandic epilepsy (peak at 5-10 years of age). The EEG shows high
Amplitude spikes in the Rolandic area (centrotetnporal region) in contrast
10 temporal lobe epilepsy (anterior temporal region). M > F. Usually noc-
turnal onset and may become generalised. Spontaneous remission in later
life (see later). z
~
Lennox-GastauHype epilepsy peaks between 1 and 4 years of age and has c
a limilar list of causes to infatrtiie spasms. The EEG shows slow and spikt: 0
waves with multiple abnormalities. · 0
co
Art acute encephalopathy will show g'!Ileralised irregular slow wave activity '<
which is independent of the cause. This phenomenon is also seen in the
post-ictal EEG.

I tptlc pathway lesi.o ns (Fig. 5.8)


Ihl1 Is a possible data interpretation q'lestion. The diagram in Fig. 5.8 looks
•llhe brain from the top.
A. lesion at the level of 1 will result in blindness in the ipsilateral eye (optic
l'llrV,e lesi~ .optic atrophy).
A lesion at
the level of 2 (the optic chiasm, often secondary to pituitary
pathology) wilt lead to a bilateral hemianopia usually resulting from a
pituitary tumour.

It

1)
0
2)
()()
Lateral
3)
()()
teniculate

~~
4)
body
Temporal
radiation

~~
Parietal
radiation

5)
Central
si::olomata 88
101
-A lesion at the level o f 3 (the optic tract). will result in a homonymous llf
hemianopia. NB The visual field defects are described accordirig to what Vc
the patient actually sees. Thus a right-sided hemianopia will be caused by til
a left-sided lesion. I
- A lesion at the level of 4 (the optic radiation) beyond the lateral genicu- I.
late nucleus will result in a homonymous quadrantic field loss. If the 1
lesion is in the temporal lobe radiation then there will be a homony· 1
mous upper quadrantic field loss and if the lesion is in the parietal lobe
radiation then there will be a homonymous lower . quadran tic visual
field loss.
-A lesion at the level of 5 (macular region of the visual cortex), occasionally
secondary to trauma, will result in central scotomata. The· macular region t,
is supplied by the middle and posterior cerebral arteries and thus a poste·
rior cerebral infarction will result in a homonymous hemianopia with
macular sparing.

RADlOlO~ICAL 'APPEARANCES IN 'NEUROLOGY:: .:c,.···. ··.' . (f<:


The aim here is to cover the more commonly asked questions that relate to •
neurology. Radiological slides occur frequently in the examination and ~
~owledge of the basics of X-rays, ultrasound, CT and MRJ are expected for •
the slides and the clinical part of the examination. t

Skull X-rays
Th.~ should only be requested in certain circumstances which include:
- I f a skull fr~ctureis suspected. Large force/area impact. Suspicious
~echanism of injury. Possibility of presence of foreign body i11
laceration.
- I f one is looking for the presence of intracranial calcification (see later for
.causes).
-Enlargement or destruction of the sella turcica by raised intracranial pre&
s~re or by a t1,1mour.

-Possibility of craniosynostosis. The expected.suture lines are absent on tht


SXR.
-Multiple punch~d-out lesions in the skull can be caused by hjstiocytosl,.
leu~emia af\d neuroblastoma.
- Wormian bones are seen in cleidocranial dys6stosis,.hypothyroidism anli
Down syndrome.
- lncrea~d density. Osteopetrosis (marf?le bone disease. Albers-Schonbet"
diseasei shows generalised increased density in all bones but is especially
well seen in the sku~l (common slide). .Remember the hair-on-end appent
102 clnCe Of bet;l thalclSSacmia major.
Intracranial calcificat·i on
· You should be familiar with the causes of intracranial calcification in pae-
. llatrics since a slide is likely in the exam or for discussion in the clinical
ICtiOn.
· I, Choroid plexus calcification in the lateral ventricles.
zC1)
: I Secondary to an intracranial bleed. c
· I lnfoctious causes: a0
• Toxoplasmosis: diffuse calcification (remember typical triad ofhydro- CQ
cephalus, bilateral chorioretinitis and intracranial calcification) '<
• CMV: periventricular calcification
• TB meningitis, cerebral abscess,.cysticercosis.
• 'lbberous sclerosis: Calcification (often seen as nodules} is periventricular
and subependymal especially around the foramen of Monro. The
~bependymal tubers can sometimes be seen as 'candle dripping' into the
fentrides.
l turge-Weber sy11drome: There is a characteristic 'tram-line' configuration
on plain' X-ray with a linear parallel configuration. This is commonest in
:the parieto-occipital region. It is not usually seen before 2 years of age.
tlyp.o- and hyperparathyroidism.
•Jttmours: Craniopharyngioma, astrocytoma and others.
\'l$allar. Subdural haematoma, extradural haematoma.
Melsresof ~ised intracranial hypertension on SXR:
'Copper beating' of the skull
Widening of cranial sutures
Thinning of the vault
Erosion of the clinoid processes.

neonatal cranial ultrasonography


Is expect~d knowledge. It is performed through the anterior fontanelle.
at coronal and sagittal scans in the neonatal unit to be familiar with the
anatomy.
the classification of peri/intraventricular haemorrhage (IVH and its
•~""~lut:Jnct~s are the commonest examination slides).

1: Haemorrhage confined to the germinal matrix.


2: Extension of grade 1 with blood in the lateral ventricle without
• rr·tr ..,.,... enlargement.
3: Extension of grade 2 with ventricular dilatation.
4: P4Srenchyffie\l involvement.
occur. in the subependytl)al germinal matrix immediately antero-
to the lateral veRtricle. Ninety per cent of bleeds occur in the first four
life. Post-haemorrhagic ventricul"r dilatation occurs in up to 40"k of
hydrocephalus above). .
leucomala.cia descnbes the progression of previously
lesions in~o periventricular echolucent cystic lesions not usually 103
visible until after the second week of life. It is associated with cerebral palsy.
There may be no evidence of abnormality on earlier scans. The cy!?ts may
coalesce.

Other cranial ultrasounds


Other cranial ultrasounds to be familiar with:
(ij
> - Hydranencephnly: Here almost all the brain ~ubstance (with the exception of
·~ brainstem, thalamus and minimal cortex} is replaced with CSF often with
:::s a normal head circumference. Babies-die SOQn after birth. NB In the exam
en there may be a slide with transillumination of a baby's skull to demon·
~ strate this. In this case there will be gross transillumination of the entm
skull. Alternatively Qther imaging may be used.
E
- Porencephnly: These are cystic cavities in one or other cerebral hemispheres,
=
w They may be in continuity w ith the later~! ventricles and are most common

-
CJ
'i:
.~
"0
Cl)
('1:1
following an intraparenchymal haemorrhage.

CT scans
0.. Remember the orientation: the image iS seen as if one is looking from the bot'
tom of the patient to the lop. Differences in X-ray attenuation mean that it il
possible to distinguish between normal tissue, infarcted tissue, bleeds,
tumour a nd oedema. cr scans are especially good at detecting blood
Contrast can be injected to show areas of increased/ decreased blood supply
and oedema.
The common views that you should use in your description of a slide a~
(1) sagittal; (2) coronal; (3) transaxial. Other descriptions that you should u~
when· referring to CT scans are areas of high or low attenua tion, referring to
lighter or darker regions respectively. High cr attenuation is caused b~
blood, bone or calcium. Comment also on the use of contrast enhanced I une11
hanced (in contrast films the blood vessels can be seen dearly and contrast h
indicated on the film).

MRI scans
These can be distinguished from cr scans by the greater definition of anato
my in the MRI scan. In contrast to cr scans lighter areas and darker areas att
referred to respecti,·ely as areas of high and low signal: T1 weighting is uS(.'II
more for anatomy, T2 for pathology. T2 ~~ighted scans show the CSF as whllt
The particular advantages of MRI over CT.of the head is the greater abillt'
to distinguish. between grey and white matter and for imaging the posterlt"
fossa. Cf scan is often preferred for looking at the chest and abdomen and
MRI for the head and limbs.
Examples to be familiar with:
- All the examples of calcification abO\·e will be viewed better with CT ~
104 MRI.
Lissencephaly: Here the brain appears smooth without the usual sulci. These
children present with microcephaly, microphthalmia, seizures and severe
developmental delay. There is a problem with neuronal migration and the
notmal six-layered cortex is not formed.
Macrogyria: The sulci are broader than -usual anc consequently fewer in z
(I)
number. c
Microgyria: The sulci are narrow and greater in number. 0
0
Schizencepllllly: There are symmetrical clefts i., the hemisphere that extend co
'<
from the cortex to the ventricle.
Be familiar with the classic CT or MR1 coronal sections of subdural and
extradural haemorrhage (in an extradural haematoma look for air bubbles
In the haematorr.a as evidence of a skull fracture).
When there is a space-occupying lesion define its location and determine
lf there is any midline shift. Remember that loss .of tissue in one hemi-
tphere may cause compensatory ventricular dilatation in the other.
A scan of raised intracranial pressure will
~ave a lack of differentiation
between grey and white matter (as in cerebral oedema), loss of gyri, and
reduced space between the skull and brain. The ventrides may also be
eompressed.
Cereb,ral atrophy_may be confused with hydrocepha.lus since in cerebral
•trophy· there is compensatory ventricular enlargement. .

Many Tela'ted questions :are asked and a wide knowledge of paediatric neu-
tOlogy ·is expected. Here ,are :the commoner paltems that you should recog-
- "these :Shonld ihelp you answer many of the questions encountered.
A child who presents with meningism (neck stiffness, positive Kemig sign
and Brodzinski sign) should alert you to the possibility of meningitis or
subarachnoid haemorrhage, but also be aware that in paediatrics there are
several other possibilities. They include: acute tonsillitis, otitis media,
upper lobe pneumonia and pyelonephritis.
Don't forget other causes of a stiff neck !Vhich include: torticollis, juve-
nile chronic arthritis and dermatomyositis.
A oommonly asked question relat~to the yo\mg child with lead poisoni"ng
who presents with one or more of the following: ataxia, convulsions, fea-
tures of raised intracranial pressure such as papilloedema and sixth nerve
palSy, mental retardation, behavioural disorders, peripheral neuropathy
and coma. In addition there ~~bdominal pain, anaemia (microcytic
with basophilic stippling) and evi~ltce of Fanconi syndrome. There may
be a clue in the history: do the family live in an old house? This relates to
the possibility of old paint flake ingestion (old paint had high concentra-
tions of lead). lead is also fOund in some Asian cosmetics (surma) and
imported medicines. The neurological features are secondary to cerebral 105
oedema, in<!reased capillary permeability and vasculitis. Avoid a lumbar
puncture (the CSF is normal but the pressure may be raised significantly)
A serum lead levd is diagnostic. Lead poisoning is discussed in mon
detail in Chapters 6 and 8. Treatment centres on reducing the cerebra
oedema, preventing fits with anticonvulsants, and using a lead chelator
such as Ca EDTA.
-The list of causes of neurological regressi011 in the older child is not a(
co> long as the number of causes in the younger child (see later). The list
·~ includes SSPE, Wilson disease (discussed in Chapter 6 and often pre·
::s senting in questions as reduced school performance, rigidity, e tc.)
U) acute psychosis, Huntington chorea and late onset metachromati~
<( leucodystrophy. ·
E - A child who presents with h)'ponatraemia and has evidence of intracranin
~ pathoiogy must be considered to be suffering from syndrome of inappro
w priate AD~ secretion (SIADH) until proven otherw~ (bear in mind thai

-u
·.::
.~
"'C
Cl)
n:s
fits and cerebral oedema among other conditions can be caused by
hyponatraemia P.er se). The possible neurological causes include meningiti~
encephalitis, head injury, cerebral abscess and intracranial bleeds. Th(
. ~vestigation and treatment is discussed in Chapter 10.
c.. - ' You may face a question that relates to a floppy infant and be given duel
which will help you narrow down your differential diagnosis. The lis
includes the following (the n.on-neurological causes are noted first): birlh
asphyxia, acute illness (e.g. sepsis), neonatal chromosomal abnormaliti~
(e.g. Down, Prader-Willi syndromes}, congenital hypothyroidism, oste6
genesis imperfecta, cervical cord trauma/pathology, metabolic problemJ
benign hypotonia. The purely neurological causes include congenital
0

myotonic dystrophy, congenital myasthenia and congenital myopathy (e.g


J!'YOtubular myopathy and mitochondrial myopathies).
- Beware the child who presents with headache mzd vomiti11g having been hJ
the GP two days earlier and been given antibiotics. The CSF shows a nor
mal protein count, normal glucose and a mixed white cell pleocytosis. Tht
answer is most likely to be a partially treated meningitis. The differenti~l
diagnosis is vir.ll meningitis or brain abscess. .Remember that it is possibl
to identify polysaccharide cell wa.lls from the killed bacteria using Jato
agglutination studies despite the fact that antibiotics have been given.
- Neonatal fits are corrurlon and you should know a differential diagnosl•
(found in most paediatric textbooks). Don't forget babies born to mothen
who are drug abusers. Other signs of drug withdrawal inclu.d e irritability
tremulousness, nasal congestion and sneezing, poor feeding, jitteriness, I
high-pitched cry and. diarrhoea as well as seizures.
- Poor prognostic features in spi11a bifida: Presence of hydrocephalus, inco11
tinence of urine or faeces, paralysis of legs, lumbar kyphosis.
-Delay in <mlki11_'? (usually achieved between 12 and 18 months) can h
1o6 caused by a whole host of causes. Bottom shuffling (often with a familY
history) and familial delay are the commonest causes. Abnormalities such
1$ congenital dislocation of the hip, weakness (cerebral palsy, muscular,
dystrophies), failure to thrive and part of global developmental delay are·
other possibilities.
Clinical features of l1ypothalamic disorders include hyperphagia, anorexia~
1leep disturbance, hyper /hypopyrexia and thirst.
Benign essential tremor is a familial condition that occurs at rest and is nab
WOr$ened by movement. Jt is improved with alcohol and propranolol.
l~·

lome question<: will make use of the fact that some anticonvulsa11t drugs
(t.g. phenytoin) can induce liver enzymes. You should be aware of the faot
that children treated with drugs such as phenytoin may develop: (a) mega-
loblastic anaemia secondary to enhanced folate metabolism; {b) rickets~ '
ondary to vitamin D metabolism. Be familiar with the reduced efficacy of
certain drugs given concurrently with hepatic enzyme inducers as well.
'l'fi..}
Fasciculatiorzs are seen in anterior horn cell damage (LMN) witn
Werdnig-Hoffmann disease,. poliomyelitis, syringomyelia, cervi·c al
tpondylosis, edrophonium test, partial denervation of a nerve root and'-
hyponatraemia and hypomagnesaemia. · !,"(• r
1
Neurological consequences of vitamin B12 deficiency include subacute c~rri-
blned degeneration of the spinal cord. (pyramidal tracts and dorsal col~
lnvolv~~ent); peripheral neuropathy; optic neuritis; a~d dementia. ,
The causes of the clinical pattern of absent ankle jerks and extensor p1a:rP
of
tar responses (that is, a mixture UMN and LMN signs) may be seen 'in:
vitamin B12 deficiency, Werdnig-Hoffmann disease, Friedreich ataxi'a~ ~r
ltsion at the conus medullaris and taboparesis. IJ no
":1"A:t1.-.-
The following drugs are associatedwith peripheral neuropathy: metronida-
aole, isoniazid, nitrofurantoin, vincristine, vinblastine, amiodar0 ne,9
phenytoin, cisplatin and AZT. "Arr:.:.
You may be shown a picture of a newborn baby with a sacrococc§iJrt
ftrntom.a which looks like a large skin-covered mass arising from the c&:·
C)"<. It may cause an obstructed labour. They are usually benign and~>tan"
Ulually be excised uneventfully.

I
ther rare clinical scenario but relatively common exam question relate:~ .
'-"""\.....
rare neurological sequel of measles called subacute sclerosing p~::, ,
halitis (SSPE). It must be considered in any child/adolescent who sb.aws-.
fllressive mental deterioration and myoclonic jerks or seizures. Be fa~iir~
'II\ the four clinical stages. ·
. r?s••N
l ltJgt 1: Diminished performance in school work, behavioural changes,
Intellectual deterioration, small involuntary movements and sometllJ!es'
filling backwards are described. '- 101

- Slage 2: Further intellectual decline, worsening involuntary movements c
and myoclonic jerks, speech and swallowing difficulties, 'muscular rigidity,
fits, focal choroidoretinitis and cortical blindness. ·

j - sPige 3: Increasing rigidity and worsening dementia.


-Stage 4: Coma and death in 1-3 years secondary to bronchopneumonia.

I
·~
:::J
lfhere may be some intermittent remissions during the course.
Onset is usually before the age of 20 (usually 4-10 years following infection •
wi.easles). Diagnosis is made clinically as well as by finding raised levels
of tneasles antibody in the patient's serum and CSF. The classic EEG iS
CJ) de~ above. The CT scan may show some cortical atrophy or low densi.'
<( ty l~ns in the white matter. Treatment is symptomatic. "
~, ~
E J ,,
n:s
>< My9~onic dystrophy tt
w ~ r
Thi:i:~ two forms. One presents at birth (neonatal myotonic dystrophy} an~ b

-
0
'i:
the~t};ler classic form presents in adolescence. The congenital form should bl ~
.~ recognised jn questions by the following features. One parent- almost invarl
"C
G) ably the mother - is affected. It is inherited as AD. Remember it is one of thl
n:s
0. dis~ which displays genetic anticipation (see Chapter 1). There may hav '
~duced fetal movements during pregnancy (indeed there may be poly
hydramnios secondary to reduced swallowing in utero). Hypotonic at birtN 1
pat;imts may need ventilatory assistan€e after birth, show impaired suckin
an~wallowing and may need NGT feeds. FaciaL diplegia, joint contracture
an@ ~pes are not uncommon. Unli!<e ~e older form, myotonia is uncon1
mon in neonates. Questions will sometimes make a note of the presence o
reflex~s to distinguish it from Werdnig-Hoffmann disease. If you suspet
necMHtal myotonic dystrophy you must examine the mother for facial wea~
neSSl;l<blyotonic handshake (slow to release) and consider an EMG (diV
bomber noise) and muscle biopsy (diagnostic). .
\~~ adolescent form of myotonic dystrophy is characterised by weakne.
w~g and myotonia, especially of the face and neck (worsened by the cold
M~a;J retardation, myopathic facies, ptosis, cataracts, frontal baldin
delayed release of grasp (manifestation of myotonia), testicular atroph
JDDM and cardiomyopathy (most die from arrhythmias). Some improve wll
quinine, procainamide and phenytoin.
Myotonia congenita describes a condition in which generalised muscul
hypertrophy (d. Duchenne that affects just the calves and is a pseudohypt
t:rBf>NSi) develops during early childhood: the children often resemble bOll
bair~rs (possible slide question). The muscles are however weak. MyotOl1
is~nt. These children remain clinically $table for many years.
l6ilin

Myasthenia gravis
.~an
hM\m,nates two clinical forms exist: neonatal and congenital.
O"· The neonatal form occurs in about 10% of all babies bom to mothers wl
l08 myasthenia gravis and about 50% will be floppy at birth. In addition lhl
y also demonstrate ,,_,eakness of facial and buJbar muscles, ophthalmople- '
1a weak cry and weak sucking reflexes. The transfer of post-synaptic
; etylcholine receptor antibodieS is responsible for the features. The babies
' 1prove over about 4-8 weeks and show a clinical improvement in response
anticholinesterase drugs {basis of the intramuscular neostigmine test).
+
z
The congenital fonn of the disease may occtir in babies born to mothers (I)
bo do not have the disease. There is a defeltt in the neuromuscular junction. c
' ll condition tl!nds to be less severe than tht! neona:tal furfu. of the disease but 0
less responsive to treatment. Anti-acetylcholine receptor antibodies 'are not 0
CQ
elected. A juvenile form also exists and resembles that of adult MG with flue· '<
ting fatiguabi:ity of muscles (muscle weakness worse after exercise).
es are affected more commonly. OCular involvement (ptosis and oph·
oplegia) and bulbar involvement are common (and may be the only pres-
tltion) but may extend to the trunk and elsewhere (including respiratory
ktvolvement). Muscle weakness tends to worsen during the day. Diagnosis
llllf be confirmed by the edrophonium test (given i.v. it improves muscle
ttllngth within a couple of minutes for up to 5 min). In addition look for the
.wence of antibodies. Treatment involves longer-acting anticholinesterases
lIIICh as pyridostigmine), s teroids, plasmapheresis and thymectomy (thymo-
ltlll are less common in juvenile myasthenia cl. the adult form). ·

Wlrdnig-Hoffmann disease or spinal muscular atrophy


U\11 is an AR disease that causes progressive destrUction of the anterior hom
till. The presentatiOJ'.l is very variable and may start in in~auterine life (mani-
lllt as reduced fetal movements and polyhydramnios) or after birth (breathing
llfftculties and poor feeding) and has a variable rate of progression. The ~arli­
the onset, the quicker the decline in function. Proximal muscle weakness,
l)'pOtonia, muscle wasting, reduced facial expression (facial diplegia) with a
haracteristic alert look, flaccid ·quadriplegia with early loss of reflexes
I f myo~onic dystrophy), bulbar palsy. predominantly abdominal breathing
IIIHawing) and a be!!-shaped chest. Fasciculations may be seen especially in
lhl tongue and later respiratory failure w ith death occurs in the first year of life.
A ~lder form exists and starts during late chiidhood and is ·called
Uplberg-Welander syndrome. There is a proximal weakness of the legs which
ftt~resses slowly over years. Normal mental function is maintained through-
t EMG abnormalities include spontaneous fasciculations and fibrillations and
uecle biopsy demonstrates group atrophy. Treatment is supportive.

enne muscular dystrophy


""- is a common question. Remember that these children may be com-
,r.t.ty normal until the age of two or even three. Points in the history to
IIJtk out for are the following: proximal muscle weakness (as in most
~athies) with characteristic sparing of the facial, bulbar and hand mus-
lill these children may have been late to start wal~ing, or demonstrate a
Wlddling gait (Trendelenburg gait); frequent falls; gluteal weakness mani-
flllltd as the Gowe: s:-gn (getting into the upright position from lying by tog
climbing up their own legs- also seen in dermatomyositis}. They have ge
eralised wasting but may have prominent calves (pseudohypertroph
caused by degenerated skeletal muscle being replaced by fat (a comm()
slide question). Kyphosis, scoliosis and lumbar lordosis are also comm~
as is bilateral pes cavus and Achilles shortening leading to walking on tit
toe. The children are wheelchair-bound usually by puberty and dea

-~ results_ from respiratory complications or myocardial involvement. Th(


may have abserit knee jerks. Increasing loss of weight is a poor prognos
sign and progression of weakness occurs rapidly thereafter. The IQ is I
·~ than 75 in about a third of qses. It is an X-linked disorder with a spont
;:,
U> neous mutation rate of approximately 30%. There is a defect in the ge
<( encoding for the dystrophin protein. Diagnosis is by finding a marked!
.. elevated CPlC enzyme level (highest at disease onset and decreases sub~
E quently) and muscle biopsy. There are no characteristic EMG finding~
n:r Becker muS<:ular dystrophy is milder than Duchenne and has a slower p~
><
w gression (alSo X-linked).

-
0
't:
.~
"0
C1)
n:r
Facioscapuiohumeral dystrophy is AD and starts at any time from child
h~ to adulthood: you should look in particular for facial weakness, esPf
dally an inability to close the eyes tightly, whistle or smile and proximl
arm weakness and wasting with winging of the scapula as the common
signs.
Q.
For completeness, the limb-girdle type of dy.s~phy affects the shouldl
arid pelvic girdle regions with proximal arm and leg weakness. It is inherit
asAR.

Guillain-B~rre syndrome and poliomyelitis


An importllr\t clinical distinction is th:at between Guillain-Barre syndrofJ
and poliomyelitis. It comes up in questions and you should be armed with tl
knowledge t!o be able to differentiate the two (see Table 5.3)_ Both conditi(ll
appear between 7 and 10 days following a respiratory or gastrointesthl
infectious illness. Guillain-Barre syn"drome is the most common acquir
peripheral neuropathy in the paediatric population and you should be fafll
iar with its Presentation. · · ,
Investigations include throat swab, stool culture and lumbar puncture, lll
acute·and COnvalescent serology samples 2 weeks apart for rising polio an
body titres. .
In·Guillain-Barre syndrome treatment is supportive including nur~h
and physiotherapy (to prevent DVT and contracture5). careful feeding M
fluid regimens, ventilatory assessment (for example, FVC 4-6 houll
and plasmapheresis. Steroids have no use in this condition, Recovt~
over several weeks to months usuaily occurs but ~idual disability II
continue.
In poliomyelitis immunisation is the best prevention. Isolation, ventiloll
assessment and careful nursing initially; subsequently, following the pyn••
slow rehabilitation and physiothe.rapy.
If a dearly defined motor and sensor! level is noted then consider unt
t10 verse myelitis. Here at the level of the lesion there are lower motor neuiiM
~ lllble 5.3 Comparison of Guillain-Barre syndrome and poJiOmyel~s

~ ""'~'"'"'"' >yndiiun< PoUomyel!rb


\ensory symptoms may be a feature No sensory symptoms
p, 'lmmetrical Asymmetrieal z
Muscle pain often precedes ihe onset of C1)
I l'lraesthesiae, numbness in toes and
flaccid p.,..... ,.._alysi$_ most c
~ muscle pain precede onset of flaccid

:J Mralysis which then a~cends. Rarer commonly~ the legs. a


proximal type affects cranial nerves,
s upper limbs and proximal ·muscles
0
cc
• lflhlally. Miller-Fisher syndro_me
~ ~ft with o_ph~almoplegia, I·
'<

lj l!flexia,apd ataxia. • ..
~ ""'l~i_s usuaiJy·over 1-2, wee~. but Paralysis is usually crver 1-2 days.
~ ll!l
t.>,e .much more rapid. .
0 Autonomic involvemen~ can occur No autonomic involvement. v
lllcluding urinary problems and cardi•c
~ 11rhythmias.
~ Motor nerve conduction studies are · Motor nerve conduction studies are
~- normal.

~
Clf findings show a ve,Y high _protell\ CSF as f~r other types'of viral
_,t(3-10 g/1) with mini.mal white meningitis.(see.earlier). Protein normal
and increased lvmphocytes. Also carry
,,.11s.
1
out paired viral titres.
i;thoiogy ·invol~es inflammation. Pathology~ .d.estruJ:tlon of
. . .rra·and·demyelination of spinal anterior horn cells.
tfirveis- near,n'e rve' root junction.
'
No Virus isolated. Virus. can be iso1A:ed from stool, throat
and CSF.
I c

(LMN) signs and dermatomal iwolvement, and -briaw the level of lesion
~ ..t~wtor,nevrpn.e,(lJMN),sigx.s. Otl}er differentials~ think about <are bot-
~ ~d myppathies. ,
,, .
tllfdau-Kieffner syndrome
! . '

1 question gives a history •f a child whose•.development .including


~nd .h mguage l"tas. beet normal but between the age of 3 and
Y,.~~c!~:v~·!RP~ ·at' abrupt d~erioration in speech to the extent that the
d m~,y ~ecome mute tlun you m1.1st consider Landau-Kleffner
~e..: ~~is-1 may- t>e a_sSO¢ittee:l' with partiar ol' generalised seizures
abot.(.\70.~ Q.f cases). The BE:; aids diagnosis>and,shoWs pos't-te·mporal
d'parietal continuous spikesand slow waves during sleep. In ~ddition
the acquired receptive1.dysp:tasia there ue a!se beruivioural and;·psy-
· t.Qr ,developmental ·-prob.ems. Treatment with carbamazepine 1and
r aAt.il!onvulsants <is disap>Ointing and steroids may be used in the
t term. •- t<- · ' '111
----·-------------------

~g%\' ~J'~~.fJ~Jr ~ bru; ,tn~m!:JV!ovni lsmo1J5rm:>b bn6 ~ia \ 1~)


~clfildllWhotpresemtS\iw.i~tacufi!ipatap@~cffi1Mtp6£taf\ttcarse~1!metfll
that in ~e case of tra1:1ma to the spinal cord a period -e'fiS~ihro~&k!"'eWS/
where there- will be predominantly lower motor neurone signs. This
replaced slowly b y upper motor neurone sign~&':V~~s,J~'¥:ie~YP»ii!di!)l'
refle:xia, upgoing plantars, loss of anal sphincter tone and possible urin•
~ti0.m0ninool\ti.ftemfe)~ortw blitb G lo '(lOt<:rrl s 2svi3 noiJz~up
b~..S.piMbceffh in\Y.olv;em~md tsy.<arly•:patltol~ maj oo~rfb'fea b by
p.flintan~~tiffnessiWithia~r.!l~glrfgJgait ~~ti~~~f IWaOOfi~~~'O\ft l
X)~~Ho..l!J>ntmenc.e anWa:onstipatioru1~k~~r -a~ rS@ns6..ye:awa rl'lo't?>r 1
~mber,1bl't>up.~ motet signgi.it tl)e:;tegs;are,morelliRely;d)\-be'}~l'fll
tb9.!f\Qiceleii0~<lumbaru'lesio~ \:no'rir'lil<et'f wprbim&lbweP'Fnl>ror' al~
in ~~:U .q<3'.ll<:! ~nnuh ~vr;v. wol2 ~m:> ~.>l'" c?u&... m"' vJ liS ''""' 1
-v~or,4~qm~{¢ssl6Jt1isJ.tusually~cauSed, hy:;~our~taBseess~56\>mt? (e.(g.
~~i-q~~YID.~) IP.r..:.the,;~:esult-.0ba1sjndi>ome~ suoli-Ja~P~.Vti\ese' may
§pinJill-iJ\..J.U! I:Q~d~ry:')in.tradural,gxbadu,:r>i~l<O't epiatrrisl! tC~sid~J:> a Nl
1'121 logram or MRI scan . Other causes include infectious transv e tlSet!fny I
above) followip g a viral illness such as chickenpox {treated with
ids), discitis, Guillai.n-Barre syndrome, hysterical paraplegia (often
define a precipitating emotional trauma). In the latter there will usu-
Y be some incongruity in neurological signs elicited . Other causes
lude 'multiple sclerosis, subacute combined degeneration of the cord, zCD
pttal sinus thrombosis, anterior spinal artery thrombosis and Friedreich
c:
2.
0
(Q
iplegia '<
Important and common question that may be aske{l is the child who pres-
acutely with hemiplegia. You should have a differential diagnosis.
Vascular malformation/bleed: Arteriovenous malformation, aneurysm,
Angioma. Generalised bleeding disorder. Look for a predisposing factor
IUGh as hypertension. ·
Migraine: Hemiplegia is usually temporary: it may also be associated with sen-
lOry changes, dysarthria and dysphasia, and there is often a family history.
lpace-occupying lesion: Subdural naematoma, extradural (remember that
lrauma is the commonest cause of hemiplegia in children - consider non-
ICcidental injury), abscess (including spread from middle ear infection),
l\unour- a sudden bleed into a tumour may cause acute hemiplegia.
Arterilll' o~clusive disease: Thromboembolic, hypertensive, arteritis, ath.ero-
Oiatous, traumatic. Venous thrombosis may be secondary to dehydration,
tongenital heart disease (polycythaemia). Plasma protein deficiencies
(luch as protein C deficiency) may also cause a hypercoagulable state.
Collagen vascular disease {SLE, PAN), sickle cell disease, Moya Moya dis-
tase -which causes progressive arterial occlusion leading to acure hemi-
plegia - seizures, dysphasia and recurrent TIAs. It is sporadic and half of
all cases are less than' lO years of age.
C1rebral disease: Meningitis (secondary to cortical vein/artery thrombosis),
JnCephalitis (e.g. herpes simplex) or post-infectious encephalitis and post-
4Dtal states .(Todd palsy). ·
vestiga~ons will include an urgent c;T scan of the brain and, depend-
the results, FBC, clotting, blood cultures, possibly EEG and cerebral
aphy.

and chronic encephalopathies


mber that neurological signs are a common presentation of a number of
Uc disorders in neonates and mtant$. They can be descriptively divided
acute and chronic encephalopathies. Acute signs to look out for ..are
, poor (eeding, vomiting, lethargy and irritability. More chronic ones
'tvelopmental delay and mental retardation which may be periodica~y
IIW'uated by acute sympto~. There may be a relationship between the
tlllt of symptoms and signs, ahd the ingestion of fat, protem or carbohydrate.. 1-13
Additional precipitating factors include stress and infection. (A fuller descrip
tion of metabolic disorders is found in Chapter 10.)
WheneYer you cH~ d~aling with a qu~bon that rdatt'!> t,, an aculr
encephalopathy of sudden onset, with or w 1thout focal s1gns. you should havj
(1)
a list of causes, but never forget the possibility o f d rug or solvent abuse. 11;
:E
:::s paediatrics the population may be divided up into older children/adolescen~
(!) and younger children. Fifty per cent of teenager poisoning is constdered ac~
cu dental and SO% intentional (experimentation or suiadal gestures). Accident
> poisoning is seen mainly under the age ot 5 years. Anything leading to poorl
·~ supervised children such as a recent. move, a new pregnancy or the absence
:::s one parent will predispose to accidental poisoning (are the family known
tJ)
<( social services?). You should look for such dues in the grey case. The co
monest drugs ingested that are fatal are analgesics, antidepressants and sed
E tives. The commonest neu rological signs are confusion, sleepiness, lethars;
cu
)( headache, vomiting, extensor plantars, focal neurological signs, seizures ar
w va rying levels of coma. In addition psychiatric features may be present such

-
(.)
'i:
.!
"C
(1)
cu
psychosis or agitation (see Chapter 10 for other features of drug ingestion). 11
differential diagnoses of encephalopathy in a child are numerous but the co~
moner ones are viral encephalitis, head trauma, drug ingestion, intracran~
bleed, space-occupying lesion and metabolic disorder (e.g. Reye syndrollll4
0.. remember also that urea cycle defects can present in older age groups. In a c,,
such as this drug screens from blood and urine will take time: the history
not yield a cause and you will therefore have to investigate the patient acco
ingly. This investigation may include taking blood cultures, FBC, U&Es, dt
screen (urine and plasma), blood ammonia, CT scan ~d EEG. Treat the pall
cautiously with broad-spectrum antibiotics, addovir, possibly dexametha&l
(before antibiotics - it can help reduce cerebral oedema), fluid restriction
anticonvulsants (prophylactically ortherapeutically).

Failure tQ reach developmental milestones


There will be questions describing a normal infant who has been develOj•
normally who may gradually ~ failing to reach develqpmental rnilestor"
regressing. In addition there may be personaLity changes, dementia and cou~
sions (associated with grey matter involvement - poliodystrophy) and II
may be weakness with spasticity. ataxia, peripheral neuropathy, dysphasl
cortical' blindness (associated with white matter involvement -leucodyst:r<ll

Causes
-Metabolic: (a) metachromatic leucodystrophy, adrenalleucodystrophy
(b) Tay-Sachs disease, Niemann-Pick disease, Gaucher
(poliodystrophies); (c) mucopolysaccharidoses in those where thcru lt
neurological involvement (e.g. Hurler syndrome); (d) abnonnal COI'I
metabolism, Wifson disease, Menkes syndrome; (e) Lesch-Nyhan
syndrome; (f) lead poisoning.
- Infection: HIV, encephalopathy, subacute sclerosing panencephalitl8
114 {55PE) (see earlier in trus chapter l
lllllllwrological: ataxia telangiectasia.
Mltcellaneous: Huntington chorea, Rett syndrome, Batten disease.
lftl of the causes named above are associated with characteristic fundo-
trlc' appearances which may be helpful in clinical diagnosis. Therefore pay
I ntlon to the fundi in examining these children. zC1)
HIV: CMV retinitis 'cottage cheese and ketchup'. c
,.lten disease: optic atrophy, increased pigmentation and attenuated a
VIISels (also have abnormal EEG and electroretinogram (ERG)). · 0
CQ
111y-Sachs and Nienumn-Pick: cherry red spot. '<
IM!d poisoning: papilloedema, ± exudates, haemorrhage.
lddition urine must be sent for glycosam.inoglycans and various blood tests
ld be ordered (ft)r Tay-Sachs: hexosaminidase levels; for Lesch-Nyhan: uric
!!A levels; caeruloplasmin levels for Wilson disease; camitine levels for fatty
ld oxidation defects). Skin fibroblast culture studies looking for various
llfll)'me deficiencies, muscle biopsy, EEG and MRI scan are other investigations.

Mtvement disorders: chorea


ftltrt are many movement disorders in paediatrics but there is one in partku-
that you should be familiar with for the purpose of exams, and that is
horea. Chorea describes rapid and non-sustained, ·non-purposeful move-
lftlrlts th~t are usually jerky and flit from one limb or part to another. They
!My come to the attention of the parents or teacher, and th~ child is character-
llttlally described as 'fidgety' or 'clumsy' in the cases of Sydenham chorea.
l'htre may be a description of difficulty in getting "dressed or eating (look for
tMH clues in the question). The causes are as follows. Sydenham chorea
Vitus' dance): a Jones' major manifestation of rheumatic fever. It may be as
ltln1 as 6 months after the acute rheumatic fever before the chorea begins (but
ually before) and therefore antistreptococcallysins may be completely nor-
lftll. F > M. There is often a period of inattentiveness before the onset of chorea.
ftltre may be 'milkmaid's sign' felt when the child squeezes the examiner's
OPJers (early sign). The chorea disappears during sleep and is often made
ne by excitement. Recovery occurs spontaneously over weeks to months.
Other causes include Huntington chorea {commoner in adults with a pos-
" ' ' family history, dementia), benign famil~al chorea, kernicterus, Wilson
"""se, during pregnancy or oral contraceptive use, drugs (such as those that
lrlcrease dopamine, such as L-dopa, and decrease dopamine, such as meto-
llopramide), acanthocytosis, thyrotoxicosis and, SLE (antinuclear antibodies
lllually positive). Athetoid movements are slow, involuntary writhing
I'C)Vements often affecting proximal limbs caused by disease of the basa] gan-
_. and most commonly by cerebral palsy.

AtPia
Another movement disorder that you should be familiar With is ataxia.
hdescribes an incoordination of movement brought about by altered sensory 115
input or a1 ered processing m the cerebdlu.rt<. l.n pc.edil:l:rics ataxia is diviC.e
up into actne, chronk and int~n:nittent iorms. RemembEr that iJcl the d;nic
i!xamination weakness and loss of musde vul~.; 1uay giv; u vvemer .....
:ippearance of ataxia and ther-efo re ch eck tu~dt; t Ower ru.;•.

Acute ataxia
-Drug/toxin ingestion: Alcohol or solvent abuse. Phenytoin, piperazine n
roleptics, various pesticides.
-Head injttry.
- Iufection: Acute cer~bellar ataxia of childhood. Implicated agen
include Cocksackie, ECHO a nd influenza viruses. It starts sudden!
usually 1-3 weeks following the infection, and resolves spontaneous!
after 1-2 months. Recent varicella infection implies varicella encephal
tis. It is rare(< 1:1000 cases) and occurs at the end or 1-2 weeks aft
the disease. Prognosis for recovery is generally good cf. m easl
encephalitis.
- Cerebellar lesions: Infarct, tumour. abscess or haemorrhage. Other cerebt
tumours such as brainstem tumours. Hydrocephalus.
- Hypoglycaemia.
- Labyrinthitis.

Episodic ataxia
- Basilar artery migraine: F > M. Family history.
-Seizures: Post-ictal state, minor motor status.
-Metabolic causes: Maple syrup ufi.rle disease, porphyria, Hartnup diseaS\•,
urea cycle disorders.

Chronic ataxia
-Ataxic cerebral palsy: 10% of all CP. Static.
-Degenerative: Friedreich ataxia, ataxia telangiectasia, Wllson disen
Refsum disease, Batten disease and metachromatic leucodystrophy.
-Neoplastic: Astrocytoma, medulloblastoma and haemangioblastoma o£ II
cerebellum.
- Other diseases: Hypothyroidism, multiple sclerosis (a rare conditio!\
childhood but may present with ataxia). Abetalii)<>proteinaemia is imJ~
tanf to pick up since it is potentially reversible with a low fat diet (
Chapter 6 on gastroenterology).
Friedreich ataxia (may come up in a grey case). Degeneration occurs mahll
in the dorsal tracts, lateral corticospinal tracts of the spinal cord and SJII
ocerebellar tracts. AR inheritance. The typical clinical features are thM
age 5-15 years cerebellar ataxia de-;-.m:;ps affecting first the lower limbs, I
lowed by the upper limbs. There is a broad-based gait. The lateral C!ll
1"16 cospinal trjicts cause spas ticity in the legs with upward going plantar!l •1
c AI column involvement causes s~nsory changes and absent ankle jerks.
· Intis and pes cavus are common. Cardiomyopathy causes heart failure
' Arrhythmias. Optic atrophy may occur. Dementia and death occur in
It age.
,.,, telangiectasia (see Chapter 9). Usually nonnal motor development
onset of the ataxia which usually begins in the first few years of life.
z
CD
l''llllilllklltor apraxia is common. Consider this in a <.hild who in addition has c
ltCUrrent sinopulmonary tract infections. · a
0
~
• I common examination question on slides or in the clinical examina-
1 It ls inherited in an AD fas~.ion with a 50% mutation rate.
l !atllll~ro1m<:ttosis type 1 (90"'1.. of cases) and neurofibromatosis type 2 (10%}.
to diagnose NF-1 two or more of the following features must b~

or more cafe..au lait patches (greater than 5 mm or 15 mm in the pre-


u .-rr.al and postpubertal child respectively). Cafe au Iait patches are often
at birth but may also appear later. Scalp, palms and soles are
• • g· Remember the differential diagnosis of cafe au lait macules (see
• •er 12).
IIIAIIIIIlarv freckling. Freckling may also be seen in the groin..
or · more neurofibromas or one plexiform neurofibroma.
IHIII• may be seen anywhere along ~e length of a nerve. They
IDttibr.orrtas
as smooth flesh-coloured pol}'p*like swellings. Plexiform neurofi-
. . .._ are found on the face and neck and tend to be more diffuse.
glioma is found in about one-fifth of cases.
or more Lisch nodules (melanocytic iris hamartomas) are seen in
one-quarter of children with neurofibromatosis.
dysplas!a of bone (often sphenoid, tibia_or fibula) .
• •• grE:e relative with neurofibro~tosis.
features include: molluscum fibrosum (skin tags) commonly seen
trunk. Additional ocular features include astrocytic hamartomas
dots on the retina) and congenital glaucoma. Additional skele-
•v••tn•~rit includes short stature, kyphoscoliosis, macrocephaly and

romatosis predisposes to the development of many tumours.


astrocytomas (most commonly), medulloblastomas, ependy-
meningiomas. Phaeochromocytomas, neuroblastomas and Wilm
l rt also more common as is medullary thyroid carcinoma.
Involvement may be caused by compression effects of neurofi-
the spinal cord or nerves. Mental retardation may occur. Renal
may be seen (and thus hypertension). The rare NF type 2 is
with bilateral acoustic neuromas. . 1117
Tuberous sclerosis
This is inherited as AD (chromosome 9) with 70% new mutation rate. (
involvement is the result of the presence of sclerotic tubers which ca1
found throughout the brain tissue. It causes seizures in infancy man
mainly as infantile spasms, later developing other Seizure types (e.g. myod
seizures). Mental retardation and developmental delay are comn
-~ Hydrocephalus may develop secondary to tuberous obstruction. The 1
manifests adenoma sebaceum, ash·leaf macules, shagreen patches a nd I
·~ ungual fibromas; cafe au lait macules are some~es~seen (see Chapter ll
::::J the eyes retinal phakomas (retinal astrocytomas) are-~n as round whibll
U) growths from the optic disc. In the kidney cysts and angiomyoliporilal
<( seen. In the heart rhabdomyomas may occur. See the .radiology section al
for a description of radiological findings. Management involves coni~
E
ca seizures.
><
w

-0
'i:
.~
'C
Cl)
ca
Blocked shunt
A common question and clinical scenario is the chlld who has a ventr
atrial or ventriculo-peritoneal shunt in situ for management of h
cephalus. The child may present with feeling generally unwell and
Q.
fever, headache, \·omiting and papilloedema on fundoscopy. The answ
blocked shunt (with signs of acute hydrocephalus) which often goes
with infection and . an accompanying ventriculitis (Staph. epider
Corynebacterium). Contact the neurosurgeons who will be able to tap the
(+ CT scan). One variation in the question/clinical scenario is to add th'
ical features of hypertension, haematuria and splenomegaly which will
you to a diagnosis of shunt nephri.tis whiCh occurs when there has
shunt in place for a long period of time (Staplz. epidermidis). C3 and C4 ar
ally low.

Pes cavus
There are a number of neurological conditions that give rise to pes c~
possible slide question). They are as follows:
-Idiopathic
- Friedreich ataxia
- Duchenne muscular dystrophy
-Spina bifida
- Charcot-Marie--Tooth disease
- Tethered spinal cord syndrome.

Raised CPK
You may be given results from a child with a raised CPK and you
know the differential diagnosis. Remember the three isoenzymes: Bll
118 MM -skeletal muscle (lhe predominant plasma form) and MB - cardUJ•
•llfferential diagnosis of raised MM..cFK includes: rhabdomyolysis, fol-
surgery, following ·muscle trauma (including following intramuscular
lon), following seizures, myositis, muscular dystrophies, hypothy·
(caused by the enzyme's reduced catabolism) and sometimes raised
birth for a few days. zCD
r:
latlon a
tilation is seen in lead poisoning. familial dysautonomia, lepro5y, con- 0
(Q
lei\SOry neuropathy and in Lesch-Nyhan syndrome (lip biting, head '<
and fingertip biting usually a~ a couple of years). Self-mutilation
y seen in a setting of global developmental delay and not on its own
1\us isolated head banging is rarely cause for concern).

locoele
~ slide in the exam is an encephalocoele. It is a protrusion of the brain
lftlnlnges through a skull defect. It is in the midline usually and occipital or
'-' position. It may be mistaken for a cephalhaematoma or haemangioma.
is required for confirmation. Treatment involves surgical removal. An
l encephalocoele is associated with the Meckel-Gruber syndf9me (see
14). .

. .
Je clinical scenario is the child aged between 1 and 3 years who has
unexplained episodes of going pale, clammy, unsteady .and falling to
r. The child iS often fearful and may cling onto the parent or nearby
. There may be vomiting following such an episode. Consciousness
Mntained throughout. The whple episode lasts about 5 min. This condi-
• called benign paroxysmal vertigo. It may recur several times a month.
JWC;arding by the parents may help in diagnosis. Differential diagnosis
include arrhythmia and syncope _(therefore consider a 24 h tape, ECG
flhocardiogram).

ln~acranial pressure
• .,lse the pattern of raised intracranial pressure in the absence of a mass
benign intracranial hypertension (pseudotumour cerebri). There may
- ol!l•••hp "vomiting and possible diplopia from a sixth nerve palsy. There
neurological examination apart from papilloedema and a normal
(the CSF pressure is distributed uniformly thus normal sulci and ven-
The CSF is normal apart from a high opening pressure. It js caused by
. . .ld absorption from the arachnoid villi. Lumbar puncture is associated
low risk of coning caused by the absence of a pressure gradient. Ninety
of cases are idiopathic but it is associated with drugs (tetracycline, cor-
_ .......,.,, obesity, Cushiz:'g disease, ~ddison dise~se. and in children rol-
atute otitis media. The main danger is of. visual loss as the blind spot 119
enlarges. Treatment involves removal of any precipitating cause, for exam
11
weight loss. Acetazolamide (a carbonic anhydrase inhibitor) may be·given

.
repeated CSF drainage may be performed. Fmally a shunt may be requireJ 111
p
Dermatomyositis
Usually presents with an insidious proximal muscle w~ (ho~
->cu weakness can~ of relatively sudden onset). There may be a positive Go
sign. Neck pain is common. The rash occurs early and is cha:racteristicall
1

·~ purple heliotrope over the eyelids which may spread down over the upt I
::::::1 trunk (shawl distribution). Gottron patches (scaly etythematous lesions) I
UJ
<( be found on the extensor surfaces of elbows, knuckles, knees and
There are characteristic nail bed telangi~ia. There can be calcinosis t
1
E calcific extrusion and nodules in the skin and subcutaneous tis$
1
cu As opposed to adult DMT there is no relationship with neoplasia. The
><
w culitic process is generalised and gastrointestinal haemorrhage is a poten
0 ly life-threatening complication. CPK is raised. An EMG and muscle bl
'i:
.- should be performed. Treatment is with s~eroids, immunosuppressives
.~ physiotherapy.
"'C
Cl,)
cu
a.. Tethered cord syndrome
You should be able to recognise the features of the tethered cord syndt
At 3 months of intrauterine life the end of the spinal cord (conus medul
lies at the same level as the end of the spinal canal. However as a result o(
ferential growth patterns, by birth the end of the spinal cord lies at L3.
months of age, because of increased giowth, the end of the spinal cord J
the level between Ll and L2 (adult position). Thus any process that intot
with the ascent of the spinal cord up the spinal canal will result in tetJ)
of the spinal cord (between the site of tethering and the base of the lll
Lesions that may cause tethering are usually found in the lumbosacral I!
and result from spinal dysraphism (interference in the process of neurvl
or fusion of the neural tube). Non-skin covered lesions ilh
myelomeningocoele an.d there is an array of skin-covered lesions incl\1
tight filum terminale syndrome, diastematomyelia and intradurallip0111
Occ'lllt spinal dysraphism describes the common disorder ~here the
processes are absent. in a vertebra, most commonly seen in I.5 and Sl ~
brae in approximately 15-30% of the population (usually found as 1111
dental finding on AXR), often with an overlying skin lesion (see later).
· Symptoms usually develop after a period of rapid growth and may b
exbated by exercise or deformity causing increased stretching of th!l
whichis:already under tension. Skin lesions such a5 hypertrichosis (comm1
dimple, lipoma and haemangioma may overlie the spinal dysraphism h1
half of the cases. Weakness of the legs with spasticity and abnormal gllll
occur. Sensory problems with paraesthesiae and numbness may 11l
seen. Structural deformities such as club foot and pes cavus are SCI111
monly. Sudden or gradual onset of loss of bladder and bowel conttlll
·120 urinary or faecal incontinence or voiding problems and constipation 111
+
1
llln· There may be reduced anal sphincter tone. Diagnosis involves the use
ultrasound (best under t.l;le age of 2 years) and ideally MRI scan which
Ul pick up the abnormally low lying cord, and will also determine the
,.lhology causing the tethering. Urodynamic studies will be helpful for
ing the degree of urinary dysfunction. Treatment involves untethering
... the success of this is invezsely proportional to the duration of time from
zCD
t of the symptoms. c
2.
0
aches (Q
'<
daches are extremely common in clinical practice. but relatively rare in
minations. However you should be able to look for and elicit the impor-
IIU discriminating details in the history and examination. The classic
llaraine consists of recurrent episodes of headache which may be preced-
.. by an aura which is most commonly visual in nature such as flashing
llhta, scotomas and shimmering lights. The headache is often unilateral
1
lid described as throbbing. In younger children the headache is more often
IMn not bilateral, nausea and vomiting are more common and an aura is
•usually described. The migraine is called complicated if there is ·pres-
- of neurological features such as hemiplegia or basilar features such as
Wlrttgo or ataxia. Remember that migraine may have been preceded by
-..rrent unexplained attacks of abdominal pain earlier in life. In children
h .ex incidence is equal but in adolescents females are more commonly
llltct~.. A positive family history of migraine is often found. 'Children
describe relief following sleep. The EEG characteristically shows slow
ve activity.
Headaches that are present on awakening, or awaken the child during
, that increase in severity and frequency over time, where there is nausea
vomiting, or are aggravated by coughing and straining are indicative of
intracranial pressure and require urgent investigation. Features on
• 111\iination that should ring alarm bells are bradycardia with hypertension
Ulhing ~flex), neck stiffness, other signs of meningism and papilloedema
fundoscopy.

ex sympathetic: dystrophy
Yt\a may be given a clinical history of a child who presents with a continu-
1 burning sensation in a part of the body with possible hyperaesthesia
leh does not correlate to the distribution of a peripheral nerve. There may
I history of previous trauma in the area of the pain (fracture or contu·
). The pain may be worsened by movement. This should lead you
ards the diagnosis of reflex sympathetic dystrophy. There may be in
jldltion autonomic features such as localised increased temperature, sweat-
" ' or erythema caused by vasodilatation. In the long term skin atrophy and
erlying disuse atrophy ma y be seen. The initial injury appears to pro-
ke a localised overactivity of the autonomic nervous system. Treatme nt
~olves physiotherapy and possibly sympathetic blockade. Many patients
llftprove with time. T21
Erb palsy andKiumpke palsy

A common b~hial plexus injury following birth is Erb palsy. It involve(


damage to the itth and sixth cervical nerve roots. This results in the uppel
arm being held adducted with the elbow extended, the forearm pronated
~t flexed Cli1j fingers extended. This is the so-called 'waiter's tip' sign.
It wtU cause an lSVmmetrical Moro reflex with absent biceps reflex. Klumpkl
-~ palsy (rare) invol~·es damage to the seventh and eighth cervical nerve rooU
and presents with weakness of the forearm and hand with an absent grast
·~ reflex. Both these types of brachial injury improve with time, usually befo~
::s the ~d of the first year. Physiotherapy will play an important role in prt
en venting contractures (passive stretching exercises).
c(

E
ca Developmental milestones
)(
w You sho~ld be familiar with the important developmental milestones undf

-u
'i:
.!!!
"'C
CD
ca
~e headmgs ol: (a} gross motor skills; (b) fine motor skills; (c) vision; (d) heal
. ~g and s~; and (e) social skills. You may sometimes be given a descrly
ti~n of a ~d ls abilities in a data interpretation. question and be expected II
gtve an estima\e of the child's age or you may be given a child in the clinlrt
exam and be e!xpected to perform a developmental assessment. One parti(
D..
lar da~ questi:on relates to the child's drawing ability: you must know llw
approxunate a!ges at which you would expect a child to copy different ima~
(see Fig. 5.9).

~·· ·~.' •. ,o • • - • ' ' • < I

Neurological 'cases are very common in the Part 2 examination. Thb


partly becausee of the fact that the~:e are many patients with chronic neu
l~gical condithons who are stable enough to be brought back time a/
t~me for exaiDrunation purposes. They also usually have excellent cli nl
s1gns. ·
. You will ne?ver be asked to perform a complete neurological examinat
10
the short caases. You will, however, be asked to perform examination
part~ of it: It : is important that you have a syste m that makes you I
conftdent 10 flrront of the examiners and enables you to pick up the cllnl
signs. In pae~diatrics the neurological signs are usually not difficult
elicit.
More than i any other assessment, the neurological examination has
co~red to a an art form. Practise it often, sin~e if you are not fluent in I~
~:-s. ffie po~~~tial of looking fragmented and niessy. There foUows a deal
ti~ of vanous.is parts of the examination: I hAtve assumed that the child l•
enou~ a~d c<l:ooperative enough to understand the requests made of rum
exa~ation ""will obviously have to be tailored to the age and cooperativll
the child conc\cemed. A description of a typical neonatal neurological ev•
tion is includ~ed.
Because of 1f the wide variation in clinical signs such as reflexes and pc
it is imp~rtantnt that throughout your neurological examination you COlli
122 the left s1de w with the right.
+
a) by2.t years

b)
0 ·-oy3years
zCD

c)

+ by4yeara X....,_ c
a
0
ca
'<

d)
D by5years

e)
6 by6years

I)

0 "by7years

g)
(j) by 10years

h)
@ by 1~years

1.9 The approximate ages by which a child sh~ ~le to draw Of' copy the
shapes.

eral inspection
Look for syndromes, dysmorphology, head ~.-ttead-shape1md -posture:
Look for visual clues around the bed such as wheelchairs or callipers.
Look at the skin for any stigmata of neurocutaneous syndromes: ataxia
'-langiectasia (bulbar and elsewhere), neurofibromatosis (axillary
freckles, cafe au lait patches, neurofibromas), tuberous sclerosis (ash· leaf
11\lCUles, adenoma sebaceum, shagreen patches and subungual fibromas),
lturge-Weber synarome (port wine stain in the distribution of the · ·
tensory divisions (mainly first) of the trigeminal nerve).

mination of the cranial nerves


hoduce yourself to the child and parent. Obse~e the face for obvious
~rmalities. · 123
I: Olfactory nerve
Usually not formally tested unless there is a .complaint of anosmia or fronu
lobe pathology. Occllude each nostril in tum and ask the patient (who has hh~
eyes closed) to tell you when he can smell - for example - a Polo mint whe~1
brought into the victnity of the nostril.

II: The optic nerve


->
ftS - Visual acuity: This ·w.ill depend on the age of the child. Remember to pu
any glasses on befo~ testing. From the age of 5 years Snellen charts mal
·~ be used. Normal ~cuity should be 6/6 to 6/9 in both eyes.
::;,
f/) - Visual fields: In a younger child this can be done by moving a small to
c( · from the peripher}' into the line of vision until the child reacts to thi;
Be careful !O be at an appropriate distance so as not to elicit a blin~
E response.. Over the age of 5 years the visual fields can be tested by con ~
=
w frontation. Sit wilh your face at exactly the same level as the child's. Then

-
u
't:
.~
"C
Q)
ftS
with your left hatld cover his right eye. Now with your right hand wiggll
your index flngef (alternatively a red pinf as you bring it in fror;n the to1
right and top left extremitiP.S towards the centre of vision (the finger shoul
be equidistant between }'ou and the child). Ask the child to tell you wh~
he can see the finger moving. In order to check the other baH of the visu6
a.. field .swap hands, that is, cover the left eye with. your right hand and thl
time your index finger of your left hand will be the visual stimulus. Y~
will assess nonn~ity by simultaneously seeing when you see your indt
finger move in frOm the periphery (your f\On-tested eye will·be closedi
This method will obviously pick up only gross visual field defects.
-Fundoscopy: You tl'lay be brought to a child with pupils already pharmactt
.logically dilated. If not you should ask the examiner if you can dim tN
lights. Depending on the child's age explain to him that he should look l
an object in the diStance and keep looking at it even if yo~ come in front l1
him: that is, to took through you. Your right eye should ·look through thl
lens of the scope to examine the child's right eye and the reverse for the lef
eye. Approach the child from the periphery and at about ~30· from th
midline, and you should be able to see the optic disc. U you are unable ~
do so, focus on a vessel and follow it in the direction in which it·gets la'l
er. U in order to focus on the retina you need a red (positive) lens, th
implies hypermetrOPia (long sightedness); a black lens (negative) impll
short sightedness-

lit, IV, VI: Oculomotor, tro<:hlear and abducens nerves


These nerves are exatni}led together. Hold the child's forehead with your I~
hand and then ask him to look at the tip of your right index finger. Ask tl
child to follow yo\lr finger as you move it in the directions that make
letter H. At each stop ask the child how many fingers he can see (testing /,
diplopia). Also look for nystagmus. Remember nysta~us is normal
extremes of gaze. It is the fast phase of nystagmus that defines:its directio
(If nystagmus is decnonstratec::t then also check hearing, check the optic fun
124 dus and do a cerebellar examination.) If diplopia is found two important rul
to be applied to determine the pathology (for a paralytic squint):
, diplopia is maximal when lookhg in the direction of pull of the affected
utclc; (b) the peripheral image is •lways from the affected eye.
Now look at the pupils and see ifthey are equal in size. Using a torch, shine
" light into one eye to look for cor,striction (direct reflex). Afferents pass via
11 MC<md nerve to the lateral geniculate nucleus and efferents pass from the
z
C1)
c
lftser-Westphal nude~ throughthe third nerve to the ciliary gan~on and
IIIWequently to the pupif~1ben sline the light in the same eye but look for a0
,e
tfllllhiction in the contralateral pupil (c'?nsensual reflex).
convergence reflex is perfcnned by asking the child to focus on an
"'ffiet in the midline which is gra:iually brought cl()S('r to the eyes. This i:::
CQ
'<

MIIOD\panied by convergence of tl-e eyes and pupillary constt iction.

'nigeminal nerve
ltnsa.tion: Test light touch usin5 a wisp of cotton wool. Ask the child to
close his eyes and to tell you eVtry time you touch them. Now on each side
of the face touch (and not strokt) the skin of the ophthalmic, maxillary and
mandibular divisions·of·the-trl5eminal nerve. The corneal reflex is tested
l pin using a clean wisp of cotton wool while asking the child to look
IWay. Quickly from the periphtry (away from th.e child's vision) touch the
cornea to elicit a blink. ·(Alwa7s consult the examiner before doing this.
They will usually tell you to skip this check as it will ~a use unnecessary
distress~ the 9illd.) ·
Motor: Ask the child ·to 'open lis mouth while at the same time applying
pressure to the chin to keep it dosed. The jaw deviates towards the side of
&he lesion. Next ask the child b bite together and then feel the bulk of the
tamporalis and masseter mu.s<!es. ·

VJI• Facial nerve


l#nsation: You will not be expe:ted to test this in the exam, but you should
know that the facial nerve SU?plies taste to the anterior two-thirds of the
longue via the chorda · tymptni branch. A parasympathetic component
t upplies the lacrimal gland.
Motor: Ask the child to raise lis eyebrows while at the same time looking
for symmetrical wrinkling of the forehead. Then ask the child to close his
eyes tight while you try and brce the eyelids open gently. Ask the child to
ahow you his teeth and to snile (a normal side can smile, the weak side
usually has flattening of the 1asolabial fold with drooping of that side of
the mouth). Again k>ok f?r S)lllDletry. A sensitive' test of function is to ask
the child to blow out his cheks and to hold them blown out while you
ptess on each cheek in tum t• see if they can ind~ hold in the air.
You must know the theory bdtind facial nerve palsies.
lasentially the upper part 'Jf the face (above the eyebrows) receives
Mlateral innervation from th! cortex. Thus a UMN lesion will cause
••uralateral weakness below he level of the eyebrows (remember that eye
llolure and blinking are not afected). An LMN lesion will cause ipsilateral 125
weaknt?ss of all tht? muscles of facial expression (including those above t
eyebrow). Remembt?r that there is no ptosis since the facial nerve contr
eye clll$ure and not opening. Thus there may be a widening of the palp
bra! fissure on the affected side. Eye opening is under control of the thi
G)
nen:e and sympathetic nervous system. If you detect an LMN facial n e
"C
::::J palsy always look behind the ears for scars or other pathology. Also look
C) tht> pinna, ~1emal auditory meatus and tympanic nwmbrane for vesicl
CG of herpes zoster that occasionally affect the geniculate ganglion (~
> Hunt syndrome). Remember that an important differential diagnosis
-~ facial nerve palsy is that of congenital absence of depressor anguli oris.
::::J
U) Cnuses offocinl nn1.•e pr1lsies:
<(
- UMN: cerebral palsy, cerebral tumour, bleed.
E
CG
- LM!\1: Bell's palsy, mastoiditis or mastoid surgery, Guillain-Barre
)( syndrome, trauma.
w -Bell's palsy is associated with oedema of the facial nerve in its intraosseou

-(,)
'i:
-~
"C
G)
C'O
route. About 80% make a complete recovery. It may be preceded by aching
behind the ear during the previous 24 h. Chorda tympani and stapedius
muscle may be involved leading to loss of taste on the anterior two-thirds
of the tongue and hyperacusis respectively. Complete facial paralysis at tl
outset is a poor prognostic factor. Neurophysiological studies may be of
a.. prognostic value (looking particularly at evidence of denervation) and
nerve conduction studies are normal in 70%. Steroids may improve the
outcome if gi\'en early. Hypromellose eye drops may be used if eye·dosu
is incomplete (to prevent corneal drying). In UMN lesions of the facial
nerve, emotion-related movement of muscles may be less affected than
voluntary movement.

VIII: Vestibulocochtear nerve


There are two components: the acoustic and vestibular parts.
By the bedside this examination is most easily carried out by asking ~
child's parent if there have been any concerns about their child's hearing
by asking the child himself if he can hear the ticking of your watch. H you S\1
pect a hearing deficit look in both external auditory canals for wax, forcl
bodies or a perforated ear drum and perform the Weber and Rinne testS
confirm whether there is sensorineural or conductive hearing loss (
Chapter 13).
Vestibular problems may be elicited by asking the child if he experienr
any dizziness. Also check for nystagmus.

IX and X: Glossopharyngeal and vagus nerves


These two nerves are intimately associated. It is extremely rare that on~
them is affected without the other. Ask the child to open his mouth and to
'Ah '. The uvula should move straight up. If there is a weakness on one $1
the·uvula will move away from the weaker side.
Next you should formally check the gag reflex; you should not, howcv
do this in the exam but tell the examiner that under normal circumstances II
126 is what you would do.
nsory nerve
lhl child to shrug his shoulders; feel the bulk of trapezius on both sides.
put the pafm of your hand on one side of the child's face and ask him to
hSI face against your hand. Feel the contraction of the contralateral ster-
•iiOJlnastoid muscle. Repeat on the other side.
z
~

IIJpoglossalnerve c
. . child to open his mouth attd observe for bulk and fasciculation of the 0
•1hen ask the child to stick his tongue out. It should of course point 0
Ul
out. A d~·iation of the tongue will however be towards the side of the '<

llnportant rule in the examination is never to cause pain to the child.


any test that you carry out, always ask the child if the limb hurts at all.
II'\ a careful and caring manner .perform your test, looking frequently at
..tlent's face to make sure that he is not holding himself from screaming.
• lb)r\ly the examiner says •examine the arms' or 'examine the neurological
ln the arms'. If you are asked to examine the anns, and if nothing is
lately obvious on inspection, 1 would then move on to a neurological
tion followed by a rheumatological examination.

n.anns .
llaprction: Look for wasting, abnormal posture, · contractures, scars or
tfWoluntary movements. An extremely discriminatory test for an upper
~~Wtor neurone lesion is to ask the patient to hold both arms out in front
With the palms facing upwards and the eyes closed. In an upper motor
twurone lesion the affected limb will gradually drift downwards and
ate. This immediately gives you important information and will
e you ·as to what you might expect in the rest of the examination.
the lesion may be severe enough so that the child may not even
his arms up•
. Hold the child's hand, and extend and flex the elbow sev~ral times.
knife spasticity will usually be easy to feel (initial stiffness followed
lr aJvlng way). Th.en, still grasping the hand, alternate between pronation
till t upinatlon. You may find it difficult for the child to relax completely
lhis may affect your tone assessment. Therefore try to distract the child
perform the tests in an unexpected, irregular fashion .
. The easiest way to do this is to put the child's arms into the position
the muscle strength you are testing. For example, if you are testing
lder abduction then put the shoulders into an abducted position. Then
the' childto hold the position and resist while you apply pressure
the positioned limb. I<now your root values for the different
actions. Test shoulder abduction, shoulder adduction, elbow flex-
11\d extension, wrist flexion and extension, fist making ('squeeze my
as strongly as you can'), finger abduction and thumb abduction .-t27
(testing flexor pollicis brevis, median nerve). In a pyramidal lesion the 0
ors are stronger than the extensors (the reverse from the legs), the typV
hemiplegic posture. There is a scale: 0- no muscle contraction; 1- fli~l
2- movement (gravitational effects removed); 3- movement against gr
Q)
ity; 4- reduced power to fesistance; 5- normal power against resistanq
:2
:::J - R4Jnes: It is important that you look confident otherwise the testin8
(!)
reflexes can become a messy affair. Hold the tendon hammer at the baSI
cu the stick part, so that there is a reasonable swing phase before the ham
.2: part hits the tendon. YQu may repeat the swings a couple of times (bul
~ endlessly) in order to observe the rimex, but be uniform in the strenglh
:::J
tn swings. If you are unable to elicit a particular reflex then you can try I
<(
.. forcement just before testing by asking the child to bite his teeth toge
or by pulling his hands apart with the fingers interlocked.
E
cu
>< - Co-ordination:
w a. Finger-nose test. Ask the child to put his index fingertip on his n<>Sf
0 and then on your index finger. Ask him to continue doing this
·c
..... alternately as you move your index finger around a plane in front (I
.'0~ the child (midway between yourself and the child). Look for intentl
Q) tremor (more marked w hen the child has to stretch to reach your
cu finger), ataxia and past-pointing. Remember that weakness of the
a.. muscles of the arm may make these movements look unsteady and
resemble or be mistaken for past-pointing or ataxia. .
b. Dysdiadochokinesis. Rapidly alternate putting the palmar and dot
aspects of your hand on the palm of the other. Ask the child to cop~
what you do.
c. Fine movements. Ask the child to put his thumb tip on the tips of r
of his fingers in tum and to increase speed as he does this. This is
useful test of coordination and function.
-Sensation: This is rarely tested in the exam. You should, however, be all
demonstrate light touch (use the technique described when testing S('
tion in the face); tv-.·o-point discrimination, pinprick (offer only!), pos1
sense (remember to hold the distal phalanx on the sides only since ol
wise you will be testing pressure and t~uch) and vibration sense.

2. The legs
The eXaminer will ask you to 'examine the neurology in the legs' or slltf
'examine the legs'. The latt-er request is more vague and sometimes the1l
nosis is made on simple inspection. However if this is not the case then
form a neurological examination followed by rheumatological exami.n~
(as in the arms).
- Inspection: Carry out a brief general inspectio~ including the surroundin~
. the child since this may give you some clues (such as the presence o.f a wl~
chair or callipers). Look for abnormal posture, abnormal involuntary tt~
ments such as fasciculations in the legs, wasting, Of the scars of pre~
128 operations. Under inspection it is always a good idea to get the child to
a few steps since this will give useful information about gait, weakness
IU\d coordination. A useful test is Fog's test in which you ask the child to
Walk qu~ckly in a straight line on inverted feet. This may bring out a hemi-
plegic posture in the upper limbs of the affected side (as he walks} and
wW thus give you information about which side the UMN lesion is. Then zCD
lheck the chiJd's back befo~ he sits down again for any stigmata of occult
c
lpina bifida.
h: This is tested in three wa~with the patient supine. {a) One can.roll ru...
a
0
Ills from side to side (a good indicator of rigtlfity); (b) By placing your hand CQ
'<
under each knee abruptly lift it upwards. The heel should remain on the bed.
II the heel raises with this movement this infers increased tone; (c) Place one
hand on the knee and the other hand around the foot and unpredictably flex
11\d extend the knee. This is a good test of ciasp:-knife spasticity {initial
hypertonia that gives way).
Pqwer: Test the power of hip flexion/extension, knee flexion/extension,
ankle dorsiflexion/plantar flexion, foot inversion/eversion. The easiest
way of doing this without confusing the child (or you) is to put the limb in
llle pOsition that you a~ testing (e.g. if you are testing hip flexion then flex
the hip and tell the child to keep it there while you push against it). Do this
lor all the muscle groups. I<now your definition of muscle strengths from
\ - 5 (see above). Also learn the root values for these movements.
Remember that in UMN lesions of the leg the extensors are stronger than
the flf?xors (giving rise to the typical hemiplegic posture). If the child can
walk on tiptoes. and on'heels successfully and without difficulty, then this
bnpties 5/5 power in the leg muscles.
ReJI~:res:
a . The use of a reflex ha.m mer is described above. Test both knees while
they are in the flexed position. Then with the knees at right angles,
hips extemally rotated and ankle at right angles, test the ankle reflex
by tapping on the Achilles tendon.
b. Plantar reflex/Babinski sign: This may be extremely uncomfortable so
warn the child first 'I am just going to ·tickle your feet'. Using a sterile
orange stick, run it along the lateral border of the sole until you reach
the ball of the foot and then stroke it medially towards the base of the
big toe. A normal respons_e is a downward movement of the big toe; an
upward movement implies an UMN lesion. Do not keep on repeating
this if you are unsuccessful at first since this will not impress the
examiner or the child! Upgoing plantars may be seen in infants up to 1
year of age.
c. Clonus: Do not fetrget this vital signo 'I1lis can be performed by
suddenly forcing the patella downwards:· that is, towards the foot with
the knee extended, or more routinely by flexing the knee, flexing and
externally rotating the hip (frog-like) and then rapidly dQrsiflexing the
ankle. More than three ~~us of d!)nus is pathological.
CQordination: This will have been tested to some degree by observing the
child walking. The heel-shin test is, howeve.w:. the most common leg 129
coordination test and consists of asking ~he child to rub his heel up and
down the contralateral shin as carefully as possible. Also test walking
heerto toe. ideally along 0\ straight line.
-Sensat-ion: 1his will rarely be asked for in the exam but you should be pro-
ficient in light touch (know your dermatomes), two-point discriminatiOf\
pinprick (offer only!), position sense (remember to hold the toe on the sides
otherwise you w!ll'also be testing pressure) and vibration (tested on bony
peripheries such as malleoli). Sensation will be particularly more difficult
to test in the younger child.

Presentlnf to the examiners


Whichever limb you are examining, start your presentation as follows:
-General observations such as presence of dysmorphic features, cutaneow
signs, pcsture. wasting. involuntary movements and gait.
-Describe the tone as normal, reduced or increased.
-Describe the power in each limb as normal or reduced (or absent). Then
may be ~ differential difference in each limb. Don'·t mention each musd
group te>ted in tum since this sounds laborious but mention in particulnt
any weaknesses, 'for example hlp flexion power was weak.
- Althou&'l reflexes have a scale ranging from 1-3 you should describe them
as nonrul, reduced, increased or absent, or present only with reinforcement
I
- Coordinttion ·is either normal or abnormal as shown by the tests pet
formed.
- Sensatiol: Mention only deficiencies in sensation.
Then you s)ould suminarise your findings by saying: 'lllese fmdings are con
sis tent witt ... .

Examinaton of the cerebellar system


It is imporant to have a routine for examining the cerebellar system whid
you have {13Ctised before the exam.
-Start at ne hands and test tone (as described earlier). You would expect I•
fWd hytt>tonia, b1,1t this will be diff!~t to elicit in a child aQd is includ~'ll
only fOF:ompleteness.
-Test for oordination as described above (finger-n~ test, dysdiadochokl
nesis ani fme finger movements).
- Examin• the eyes for nystagmus (as described above). Typically nysto
mus is }')rizontal in cerebellar lesions.
- Ask the:hild to speak and possibly to repeat several words.suCh as ' hlj
popotar.us' in order to demonstrate d~sarthria. In cerebcl1ar disease II
130 child's s>eeCh SO\Uids drunk and explosive at times.
'd- Ask the child to walk.. In cer~llar disease there is typically a wide-based
gait with the arms held out wide. The gait is ataxic and the child will tend
to stagger towards the side of the lesion. This may be accentuated by the

J
el
heel-to-toe tesL Incoordination maybe caused by cerebellar disease or pos-
n, IJerior column disease. "Ole posterior c:olumns carry information about
vibration. position sense and IIOuc:h. The spinothalamic tract carries infor-
z
~
'l mation about pain and temperature. c
11 0
' - Romberg's test is a test of cerebellar dysfunction and posterior column 0
(Q
disease. Ask the child to stand with his feet ~ogether and then to close
'<
his eyes. In cerebellar disease there may be truncal ataxia with the trunk
swaying in an attempt to stay upright with the feet together (even with
the eyes open). Howevec in posterior column disease the patient will
become unsteady only when you ask him to close his eyes, thereby
removing any visual clues that be is using to stay upright (since propri-
oceptive input has been lost). For causes of cerebellar disease, see
before. · ------_,___

~
11 Proximal_~thy
11
there are a number of important hereditary muscular dystrophies and
tnyopathies that present with proximal myopathy. Have a screen for tes'ting
'II lor its presence.
- ~ the child to put his hands in the air (m the history they may
complain of not being.able to comb their hair).
- Ask the child to stand up from abe sitting position.
- Ask the child to get on to the ftoor and then stand up (in order ~o
demonstrate Gower's sign).
- Ask the child to lie down and to sit up without using his arms.

- Hmtipkgic gait: The affected leg is rigid with knee extended, hip adducted,
ankle plantar flexed and foot inverted (that is, pyramidal pattern). In order
to move forwards the foot descnbes a semicircle and the toe scrapes the
ftoor: this pattern is called circtimduction.. In hemiplegia the arm w ill also
be in the typical pyramidal pattem with the elbow flexed, wrist flexed and
pal.tnar/finger extension. ·

- Panzplegic gail/spastic diplegitt: This classically causes the scissoring gait, and
the chi.ld uses.his hips primarily for movement. The knees are partially
Hexed. This is often-called the 'waddling through mud gait'.
- Waddli11g gait: Here the pelvis drops on each side as the foot of the same
side leaves Ute floor. This is caused by weakness of the pelvic girdle
muscles.
- Snrsory aMritz (dorslrl column loss gait}: This is classically a stepping or
stamping gait. There is a wide-based gait and· the patient looks intently al 131
~
+
the floor since he relies on visual dues as his proprioceptive input has been
lost. One cause of this is Friedreich ataxia.
-Drop foot gait: This occurs when there is an inability to dorsiflex the foot.
QJ Thus the foot and the leg on the affected side have to be lifted higher in
:2 order to avoid t,.itting the floor. Possible causes include Jamal popliteal
::s nerve palsy, poliomyelitis and peroneal muscular atrophy
(!)
->
C'G
(Charcot-Marie-Tooth syndrome).

·~ Neurological examination In an Infant


::s
en Becau.c;e the infant is still developing motor skills, part of the examination will
..
<( also look at development.
E
C'G Inspection
)(
w - Undress the infant to the ~ppy. Look at the posture of the infant. See if he

-CJ
·.:::
.!
'0
QJ
C'G
is moving all four limbs. If the baby is crying, is this of nonnal sttength and
pitch? Are there any abnormal movements?
- Since it is going to be impossible to assess power formally you must pay
attention to movements and in particular look for antigravity movement$
Q. - Look at and feel the fontanelle.
- With a bright object see if the infant can fix and follow.

Tone .
-This requires experience b!Jt take .both of the infant's arms in your handl
and push and pull them in all directions in order to.get an idea.of the tOI\f
and power. This is usually strongly resisted by the baby. 1llen do the san1t
with the legs.

Reflexes
- Don't use a reflex hammer unless the child is over 1 year of age. Before thl
you can use your fingertips to-elicit ~e reflexes. You·may perform a few I
the other reflexes such as the Moro (may persist in ce,rebraJ palsy),· grllt
reflex, rooting reflex, asymmetrical tonic neck reflex and placing or sl~l
ping reflex, all of which usually disappear by 3-6 months. The parachlllf
reflex appears at about 6-8 months. You should be looking for the prescn
and symmetry of these reflexes.

Developmental screen
-Place the baby in the. prone posi~on and observe to see the degree of h•
lifting and posture of the back.
.-.:..Then perform ventral suspension: ·
_:Then pull the baby to sit by pulling the shoulder tips forwards and I
from the hands (looking for head lag).
't32 -Examine the back (for stigmata of spina bifida).
' •llnlne the cranial nerves. This
has to be done in an opportunistic fash·
,._lnd you will not be able to do this systematically. For example, seeing
INI lhe baby has a symmetrical smile m\<1 closes both eyes normally and
• fNwna implies that the motor division of the facial nerve is intact. Look for
' MnNI ~movements. At the end of the examination you will tell the zCD
1
••llr.er
that you would also 1i1ce to also examine the gag reflex. corneal
and perform fundoscopy for coa~pleteness.
c
0
0
CD
'<

.,
d

133
astroenterology
6
"-!iatric gastroenterological problems are cotnmon in clinical practice and
ills reflected in the large number of questions that relate to it in the exam-
lfllton. I have attempted to include most of the question possibilities that you
Ht)lkely to encounter as well as useful background information.

are many paediatric problems that may arise from abnormal e mbry-
development and it is important to be familiar with these. lhe examina-
• now ~ms to place a greater emphasis upon the basic science knowledge
•anclerlyii1g paediatric conditions.

phageal atresia
~about 4 weeks of fetal life the foregut is separated into a ventral part called
respiratory primordium and a dorsal portion, the oesophagus, by an
'*<>phagotracheal septum. Oesophageal atresia is thought to occur as a result
fll I posterior deviation of this septum. The most common variety (85% of
eormaJities) consists of a blindly ending proximal oesophageal segment
with the distal segment usually coiU1eeted to the trachea by a narrow fistula
bove the bifurcation. Other possibilities include no fistulous connection

!: een the oesophagus and trachea (8%) or there may be an H-type fistula
re there is a non-obstructed oesophagus and a fistula half way dO'If\.'1'\ the
IIP'ea (5%).

lltestinal embryology and malrotation


Daaring normal development the primitive intestinal loop herniates into the
-ilical cord between the fourth to the fourteenth weeks of fetal life. The
1feX of this loop is in continuous connection with the yolk sac via the vitelline
epct. In about 2% of people a remnant of this d:uct may persist in the form of
a Meckel's diverticulum and may contain ectopic gastric or pancreatic
tgucosa causing ulceration, haemorrhage or act as an apex of an intussuscep-
lbt. If the vitelline duct remains patent there will be a fistula between the 135
lum~': of the ileu~ and the umbilicus and faecal discharge. may be seen at ~ ~viati?n of the urorectal septu~ ~ a <brsal direction causes ano. rectal age. ~­
umbthcus. Vitelline cysts may also be present in the site of the previo~
vitelline duct. The midgut loop rotates 270" antidockwise around the superio
•IS
which can be of two types_: tn ~tgh 1ypeS the bowel ends above th~ pelV1c
ftoor and in low types ~low tt. Htgh ty_p~ comm~nly have ft.St~las mto the
mesenteric artery. The proximal part of the jejunum is the first part to retun vagina, bladder or urethr~ (usually _no VJStble anus IS pres:ent at bu-th and t~e
into the abdomen and occupies the left side of the abdomen. The colon is t1\ presence of one not continuous wtth the bowel would 1mply rectal atresta

-
(i)
last part to relum. The failure of the intestinal loops to return to the abdomf Which is very rare). D)

- nal cavity will result either in an omphalocoele (exomphalos) covered b


amnion, pr in gastroschisis (no covering) (see later .yt this chapter). Hlrschsprung disease
...
(/)

0
.~ ~
::l
c:
::l lncomple~e rotation
There is 'a failure of the autonomic ganglion cells {the submucosal and myen· ;-
...
ltric plexuses) to reach the hindgut regton at about 4-7 weeks of fetal life. This
U) 0
<(

E
returning first to produce a left-sided colon witli the small bowel on the
side.of the abdomen. The small bowel in this case has a very narrow mes('l
ri,
This occurs when o~y 90" of rotation occur$ with the colon and caecur failure results in the area involved being tonically contracted producing
obstruction (see later).
0
CQ
'<
CG
)( teric attachment and can be prone to volvulus and subsequent infcuctiO'
w NUTRITIONAL STATUS · · · , · , •. · · . · ·-
Sometimes there is reversed rotation of the gut with a 90" clockwise rotatlt

-(.)
'i:
.!!!
"'C
Cl)
CG
such that the transverse colon passes and lies behind the duodenum a~ !Methods of assessing nutritional
superior mese,nteric artery. Arrested caecal deScent describes the case w~ lltVeraJ available and include the folk,wing.
status in children

the caecum remains in the subhepatic position and may result in the prodll - The simplest and most commonly used in the clinic would involve a
tion of Ladd's bands which are abnormal peritoneal bands that may ca
are important. There are

detailed history of diet over a typical period of time. This itself may reveal
0. neonatal bowel obstruction involving the second part of the duoden significant nutritional deficiencies.
There is also a possibility of recurrent volvulus later in life, again caused 11f
narrow _n;lesenteric attadunent (see later). Growth charts of height, weight an:i head circumference (particularly serial
me~~rements) are easy to obtain and are very usefuL· ·
hrtestinal s~nosis and atresia Measurements of mid-ann circumference and triceps and subscapular
skinfold thickness give·an indica:ion of the body build of the child and
These are the result of interference in the normal process whereby the these values can be compared with standards for age and sex.
intestinal segm.ent vacuolates and forms a lumen. The commonest site ~
duodenum and this produces a distension of the proximal duodenum laboratory investigations can also be used and in particular mineral and
very underdeveloped distal segment (see later for presentation and electrolyte concentrations can be assayed. Protein malnutrition can be
ographic appearances). assessed by measuring the plasma proteins such as albumin (hall life of
about 20 days) and transferrin (half life of about 10 days), as well as deter-
mining the ratio of albumin to globulin which may decrease in protein
Dupliea~ion cysts
malnutrition. · ·
These may occur anywhere in the gastrointestinal tract but are most t should be familiar with the advantages of breast feeding to (a) the baby
monJy seen in the ileum (mesenteric side). They are either double rtll'll• , .llftrl (b) the mother. This information is available in most paediatric textbooks.
encysted in nature. The encysted variety may be in continuity with the Ut••-•111&
lumen. The mucosa of these duplications can be of gastric or pancreatic
and bacterial overgrowth may result. Obstruction may be seen.
should know about the constituents of breast milk. There have been ques-
-Mindgut abnormalities asking for approximate values, but even if these are not committed to
_.._,I\Orv one should be familiar with the main quantita~e and qualitative
The hindgut ends in a membrane called the cloacal membrane, an .Uifer>enc:es between the varieties of milk (see Table 6.1).
lined cavity which is in direct connection with the ectoderm outsidr
cloaca later divides into an anterior primitive urogenital sinus and a constituent summary
anorectal canal separated by the urorectal septum. At the distal end 1ol main carbohydrate component in all the types of milk is lactose. It is easily
anorectal canal lies the anal membrane. In simple cases the anal cannl ._SniDie and fermented by the lactobacilli in the gut to produce acidic stools.
136 blindly at the anal membrane (which usually breaks down at 8 main protein in breast milk is whey, which is more digestible than the '137
~uu should ~familiar with th~ mctlnutrition syndromes and the clinical con-
Table 6.1 Comparison of the constituents of cftfferent types of milk
wquenCe$ of mineral and \'itamin Jetici~ncies.

calories (g) 70 67 65
Protein (g) 1.1 3.3 1.6 IIIOCHEMICAL ABNORMAUnES CAUSED BY , · ._ ·: .
Caseln:whey ratio 3:7 8:2 4:6 t,ASTROENTEROLOGICAL CONDITIONS · · ·,_. · .
fat (g) 42 3.7 3.3 llwse commonly come up in many parts of the examination and you should
-~ Sodium (mg)
Potassium (mg)
Phosphorus (ng)
15
60
15
52 .
140
98
21
70
49
1111 familiar
with them.

·~ ca~um ("!g) 35 120 55


VOmiting
::J
en Low sodium, potassium and chloride.
<(
.. ~ow's milk ~rotein casei~ (which is more likely to curdle). The other proteiN
E m breast milk that. are tmportant are the immunoglobulins lgA and IgM, lttrsistent vomiting or hypertrophic pyloric stenosis
CIS
>< lysozyme, lactofernn and lactalbumin, which are important in immunologi·
w ca~ transfer. Ljrmphocytes and macrophages also add to this protection. Hind ... also later in this chapter. Hypochloraemic or hypokalaemic metabolic alk.a-

-
u
·.:
.~
"C
Q)
CIS
m1lk at the e:1d of a feed contains more fat than foremilk. Breast milk has
lower levels cf vitamin K (thus haemorrhagic disease of the newborn is more
li~ely) but ~Ere are higher levels of vitamins A, C and E compared with cow's
null<. No~e m Table 6.1 the relatively lower levels of sodium and potassium in
IDII.s. The urinary pH, contrary to w hat w~uld be expected, is usually acidiC.
nus is because the kidney conserves potassium in preference to hydrogen ions.
Remember the other possible causes of a hypochloraemic or hypokalaemk
metabolic alkalosis that should be considered (this is a common question) and
beware: they may have similar clinical presentations. It can be caused bv renal
0. b reast null< c:>mpared to cow's milk: this means that hypematraemia is less
likely to produce a problem in the breast-fed baby. Colostrum is the milk that end extrarenal chloride loss. The causes are Bartter syndrome, cystic fibrosis.
is produced i:\ the first 48 h after birth and is straw coloured with a high pro hloridorrhoea, diuretic or purgative abuse or p rolonged v.omiting due to any
te~ conte~\ and l~wer fat and carbohydrate content compared to normal ause.. Hyperaldosteronism should also be considered.
milk. The mt:'Odu~on of bottl~ c~w's milk is deferred until the age of 1 year R~member that if vomiting is severe there may also be evidence of dehy-
because of tre low 1ron and Vltamm c:;ontent and the risk of chronic subclinl dration with raised urea, hypematraemia and possibly raised haemoglobin.
cal gastrointtStinal bleeding. There may also be hypoglycaemia .
The avenge calorific requirem'l!nts for a 1 month infant are approxl
mately 100 ~cal/kg/day. Standard cow's milk formula contains abou1 "-labsorption syndromes
100 kcal/100 ml.
Malabsorption syndromes can cause low iron, calcium. phosphate, ferritin.
Albumin and red cell folate levels, and raised ALP and INR levels. Hepatic
Contraindi:ations to breast feeding holestasis results in reduced fat absorption and of the fat-soluble vitamins A,
Maternal D, E and K. Thus vitamin D malabsorption can cause rickets and vitamin K
malabsorption a raised INR. Reducing substances in the faeces gives an indica-
-Untreated maternal TB. lion of carbohydrate malabsorption. Faecal AlAT collection can assess protein
- Matemalhepatitis B SAg +ve. lbtlorption. and elastase in the faeces is a specific marker of pancreatic function.
- Matemaldrugs such as arniodarone, cytotoxics, indometacin, lithium,
tetracycliles. theophylline, colchicine, senna, carbimazole,
chloramrhenicol, dapsone, thiouracil and sulphonamides, all of which Abckm1inal pain and hyponatraemia
are secreed in significant quantities in breast milk. ll\ls syndrome pattern repeats itself time and time again in questions and vou
-Maternal HIV infection. This is not the case in Third World countries lhould be familiar with the causes. lt is discussed in the section under clm"ical
where tte risk of death from malnutrition is greater. lftnarios later in this chapter.
Neonatal
Diarrhoea
-There ar. various congenital anatomical abnormalities such as cleft lip
and palcte. Hypo/hypematraemia or normal serum sodium. The potassium may be
100 lnbom <l'rors of metabolism such as phenylketonuria and galactosaemlll Nlsed initially because of the metabolic acidosis secondary to bicarbonatE '13g
loss, but if the diarrhoea is persistent it invariably falls. The g lucose may ini·
tjally be raised and this may cause some confusion with d iabetes mellitu~ emU. .
(DM) in s~m~ questi~ns. Testing the stools for reducing substanc~s is usdui AMemia can be caused by a wide range of gastrointe:stinal pathologies.
Q) to detemune if there 1S sucrose/lactose malabsorption (faecal pH may also~
:2 low because o f bacterial fermentation). loss
::l Remember that excessive mucus production by the bowel can pro.sW& a nor· causes a typical iron deficiency anaemia pattern (see Chapter 8). The fol-
(!)
mal anion gap metabolic acidosis (like renal tubular acidosis, inges~on of HCl t.wtng should be.considered: reflux oesophagitis, oesophag~al varices, pep-
cu ~~ in waemia and in ureteric djve~n into the sma1l boWel). The bio- ulceration, gastritis, cow's milk protein intolerance, infl~tory bowel
> dlerrucal picture of an extremely low plasma chloride an(!" potassium and rugh , haemangioma or telangiectasia (look for telangiectasia elsewhere),
·~
::l
plasma bicarbonate should lead you to suspect congenital chloridorrhoea cause<llltlekel's diverticulum and chronic NSAID administration (e.g. for chronic
en by.abnormal active chloride absorption in the ileum. Confinn it by finding very lllrltides). Worldwide, the hoo1cworm is the commonest cause. Remember
low urinary chloride and plasma levels and excessive faecal chloride levels (usu . . an acute bleed may not have any effect in haematological indices initially
..
<(
ally more than 100 mmol/1 with a normal range of approximately 5-15 mmol/1~ wtldn a few hours.
E
cu It presents early and is often associated with hyperbilirubinaemia. There ~ ·
>< growth and developmental delay. Treatment consists of potassium chlorid uced red cell production
w (KCl) replacement (this may occur in a data interpretation ques~on). other gastrointestinal causes of anaemia are induced by reducing red cell

-
u
•t:
.!
"C
Cl)
cu
The following is a useful classification.
••••
. uction. The main ones are vitamin 812 and folate d eficiencies which
a megaloblastic anaemia (see Chapter 8). The vitamin 812 intrinsic fac-
mplex is absorbed in the terminal ileum.
\lrtnmin 812 deficiency can be caused by achlorhydria (possibly as part of
c.. ~cious anaemia) where there is reduced intrinsic fa~r production
Malabsorption as a result of mucosal damage tderived from parietal cells), fish tapeworm infection, terminal ileal resec-
- Coeliac disease: Mainly proximal small bowel affected with mucosal da111 ~~on··m. terminal ileal diSease suCh as Crohn disease.
age decreasing in severity towards the ileum as gluten is degraded lolote tkjiciency: Folate is absorbed in the proximal bowel and its absorp-
smaller and smaller non-toxjc fragments. will therefore be affected by proximal bowelopathies such as coeliac
- Crohn disease which can affect any part of the small bowel but has a propt ~· Chrome diarrhoea states can also produce folate deficiency by a
sity for the terminal ileum (vitantin B12 and bile adds). llcondary deficiency in the intestinal enzyme necessary to convert d ietary
..te into the absorbable form.
- IntestiMl lymphangiectasia where the intestinal villi are dHated either cc
genitally or secondary to obstruction (see later).
of an abnormal jejunal biopsy
- Abetalipoproteinnemia (see later).
taken a jejunal biopsy in the investigation of malabsorption and
a histological ~rt of villous atrophy the differential diagnosis is
Intraluminal causes of malabsorption asked for.
-IntestiMl hurry such as may occur post gastrectomy or ileal resection. possibilities are:
- Defective secretions intc the gut: (a) cholestasis resulting in decreased 111 M•IJac disease. For a definite diagnosis an initial biof>$y is req~ fol-
tinal bile salts a nd thus defective fat absorption including fat soluble v • twtid by a normal one 6 weeks' later, following a gluten-free diet. A third
mins; (b) pancreatic enzymes: cystic fibrosis, chronic pancreatitis ami • • llliiiU!tiJlrtes taken following a challenge of gluten (rarely required nowa-
Sh wachman-Diamond syndrome (see Chapt~r 14). Remember that in children under 2 years of age repeat biopsy is
important since transient gluten intolerance ¥t more common.
-Infections: Giardiasis is the commonest but consider also Strongyloidt
hookworm infestation.
are
~Hltv..-llv studies also useful (see later).
-.n1~r.arv gluten intolerance is usually secondary to gastroenteritis.
- Bacteritzl cvergrowtlz: Typically in blind loops but also in duplication 1,
can classically produce fat and vHamin B12 malabsorption.
's milk/soya milk protein intolerance. 141
-Enzyme deficiencie.s: the commonest is the disaccharidase/lactase defat 1
140 but also others such as congenital lactase deficrency.
-Giardiasis. jugated hyperbilirubinaemla
"*'jugated bilirubin is water ~luble and ~-thus no bilirubu;,~::;:
- Severe combined immunodeficie~cy.
jiM (acholuric jaundice). There 1S how~ .an snaeased amount
- Post chemotherapy. finDgen in the urine.
- Hypogammaglobulinaemia (althousl} this may be secondary to complic,
ing giardiasis). led bilirubin production .
-~ ·~~in the tropics.
Haemolysis for any reason: extracellular (itYnmme, drugs), mtrathcellular
(red cell membrane defects, haemoglobinopathies- after 6 m~~ s of
·~ -Tropical sprue.•'fl\alabsorption syndrome encountered in the tropics. lp) and red cell enzyme defects (G6PD deficieftcy, pyruvate mase
:::J
0 Following a jejunal biopsy 1here are other histological possibilities that m llefic.iency) . .
be considered. In giardi.a:.-is itis occasionally pos&ible to~ organisms. If llps1S: congerutal or acqwred
..
c(
cemed about a disaccharidase de6ciency then various histochemical ~ lllematoma .
E technh:jues can be carried out to Cfmfirm this. In abetalipoproteinaemia- ( folycythaenua.

=
w
later for details) characteristic swollen and fat-laden epithelial cells can
ued bilirubin uptake or metabolism

-
found. In intestinal lymphangiectasis dilated mucosal lymphatic.vessels
u be seen (see later). Gilbert syndrome
·.::
Occasionally there is a slide of a jejunal biopsy taken from a child wl Crigler-Najjar syndrome
.!!! coeliac disease. The characteristic features are: Lucey-Driscoll synt!~m~
"C
G)
)Jypothyroi~
C'CI 1. Villous atrophy which diminishes in severity the more distal the intestitl
a.. Sepsis, acidosis ~d hypoxia
2. Heavy infiltration of the lamina propria with chronic inflammatory cd Coogestivecar~c~wre
(lymphocytes and eosinophils). Physiological jaundice of the newborn.
3. Elongation and deepening of the intestinal crypts.
~lelred enterohepatic circulation
lreast milk jaundice
HEPATOLOGY ,. . ·, -~ ·: ·~ ~ . - ·-i . : · , .~ .. _:,
~ustinalobstruction

Bilirubin metabolism Receiving antibiotics.

This is a prime example of a basic science topic that will be popular w


examiners; it is extremely important in understanding many clinical con Jugated hyperbilirubinaemia
tions in paediatrics. . . . l1illlntrahepatic causes produce a mainly mixed picture (with c'?njugated and
Post-mature erythrocytes ~.removed by the reticuloendothelial sys tem . d h rbilirubinaemia). The extrahepatic cholestatic causes pro-
globin broken down to amino acids and iron reutili.sed ~haem~ bilivel\l ~}uga~el ~ ted hyperbilirubinaemia. .Bi.liJ»bin will be found in the
(water soluble)~ biliverdin reductase (all tissues)~ unconjugated bill :a(~m y CO~JUS:ed bilirubin is water &aluele). ~~
bin (water insoluble) ~ transported to the liver attached to albumin dsmcke c~nJugad tools and pruritus
·· · _ . ar unnean pa1es ·
b1hrubm taken up by the hepatocyte membrane and transported to -r--·
smooth endoplasmic reticulum (by carriers such as ligandins) ~ UDP B
curonyl transferase ~ conjugated with two molecules of glucuronic acid Neonatal hepatitis syndrom~ .
bilirubin diglucuronide (water soluble) ~ actively transported into the t Congenital infection, e.g. rubella, CMv. toxoplasmosiS
·canalicUli~ bile in the inl'es'tine '~ in-~tminal ileum hydrolySced by' l:>ach Metabolic: AlAT deficiency, cystic fibros~. ..~0 metabolism: ~
to release free bilirubin ~ reduced to urobilinogen which has ~ fo Daemia (test for reducing substances), fructosaemia, glycoge~ storage diS-
(1} most of it is oxidised to sterco!:>ilin (faecal pigment); (2) SQme is absor' ease type IV. Protein metabolism: tyros~ Lipid ~~lism: Wolman
by the terminal ile~m and transported back to the liver by the enteroheJ• disease. Storage diseases: Gaucher disease. ~h~1Ck disease. €opper
circulation; (3) some is reabsorbed by the blood and is excreted in the urlt lnetabolism: Wilson disease
You must know the following classification. I have included neonatal
childhood causes of jaundice. Idiopathic giant cell hepatitis. 143
·142
Abnormalities in excretion of bilirubin by the hepatocyte
- Dubin-Johnson, Rotor syndrome. ....
ftte baby referred to hospital with jaundice at 3 weeks of

nus is another common question. The causes of prolonged neonatal jaun-


Non-neonatal hepatitis dke must be divided up into conjugated and unconjugated hyperbilirubi-
-lnfection: This includes the hepatitis viruses A, B, C and ECHO, Reo, CM naemia. Of course a detailed history and clinical examinati~n ·would be
EBV, Leptospirosis. ••pected.

->
C'G
- Chemical and drug induced: Carbon tetrachloride, ethylene glycol (includl - Conjugated hyperbilirubinaemia causes include the conditions under the
other solvents such as in glue sniffing), alcohol (ethanol and methan(l titles neonatal hepatitis syndrome, intrahepatic and extrahepatic
·~ halothane, isoniazid and rifampicin, paracetamol, methotrexate. cholestasis and disorders of bilirubin excretion (in jaundice classification
::::J -Autoimmune. above).
U)
c( Unconjugated hyperbilirubinaemiD causes include hypothyroidism,
Intrahepatic cholestasis haemolytic anaemia, breast milk jaundice, sepsis, Gilbert. syndro~e,
E - Alagille syndrome (see Chapter 14) Crigler-Najjar syndrome, Lucey-Driscoll syndrome and transtent famil1al
C'G
- Byler disease (progressive familial intrahepatic cholestasis- AR) hyperbllirubinaemia.
~ - Zellweger syndrome (see Chapter 14)

-CJ
·.:::
.~
"C
Ci)
C'G
- TPN cholestasis (mechanism unclear).

Extrahepatic cholestasis
-Biliary atresia, choledochal cyst (typically a variable jaundice), mass/r..
lnvestigatbns: Initially: FBC, blood group and direct Coombs' test, liver
function tests including a split bilirubin estimation, U&Es, blood culture,
urine for MC&S, urine for reducing substances, TFis. These will be useful
for an initial screen, and if the jaundice tums out to be unconjugated and
the other tests are normal (and the baby is clinically well) then a wait and
D.. plasia, stone, high intestinal obstruction.
tee policy is usually recommended. H the mother is bre~st feeding then this
There is a wealth of questions relating to jaundice in the paediatric examt will be' the usual cause.
tion and we will endeavour to cover them now in their various fonns thl'O\f a
Ho.;..,ever if there is conjugated hyperbilirubinaemia then the neces--
examples. We will refer to the classification above throughout. sary biochemical and serological tests must be carried out as soon as pos-
sible to exclude the aforementioned causes. Initially liver function tests,
The baby who presents with jaundice on the first. day of life bacterial and viral cultures, metabolic screening tests and hepatic ultra-
&Ound will be organised. After these have been performed, and if there.is
A baby who presents with jaundice on the first day of life is always abnor~ still no specific cause found, it is imperative to differentiate between bil-
You must know that the causes include the following: iary atresia and idiopathic neonatal hepatitis, usually with radioisotope
atudies and possibly a liver biopsy. In extrahepatic biliary atresia (which
Haemolytic causes may also present with d eranged clotting, raised transaminases a~d a
- Blood group incompatibilities: Rhesus haemolytic disease, ABO incompah raised ALP and GGT) there is delayed excretion of radioisotope into the
ity, and anti-C, E, I<ell and Duffy haemolysins. extrahepatic ~ucts and intestine. The 99Tc labelled 1-UDA scan is used
- Red cell membra~ defects: Hereditary spherocytosis. with less than 5% excretion of the drug in 72 h. The rose bengal test is an
older method. The need for rapid diagnosis is because any delay in the
...._ Red cell mzyme defects: Glucose-6-phosphate dehydrogenase defid Kasai procedure (see below) beyond about 6 weeks of age reduces its
(commoner in black, oriental and Mediterranean peoples). Remember chances of success. NB In biliary atresia the onset of jaundice may be
haemoglobinopathies (such as sickle cell disease and thalassaemia) clelay~ for up to 4 weeks after birth.
not present in the neonatal period since fetal Hb predominates.
ICAsai procedure:· A hepatic portoenterostomy. This involves' forming a con-
Sepsis . nection between the porta hepatis and the bowel lumen. Postoperative
Septicaemia, UTI, congenital TORCH-like syndrome. complications include: intestinal obstruction, ascending cholangitis (early
and late), peristomal breakdown and progressive biliary drrhosis. Success
- Investigations therefore include: full blood count, blood film, blood 8' of the operation js judged by an improvement ··in biliary flow.
of baby and mother and any atypical m aternal antibodies, direct Coon Approximately 50% of cases are unsuccessful with ongoing inflammation
test, G6PD assay depending on the ethnic group of parents, lPRCH St and biliary cirrhosis. Consider liver transplantation as an alternative
especially if conjug ated hyperbilirubinaemia present. Infection 5(' 1 145
option.
1M (blood culture, urine fo r MC&S and so on).
Remember that in the exam you should be able to discuss a full differential
A baby found to be jaundiced on the second clay of life
diagnosis and list the other questions that you might like to ask in the history
Hb 16.2 g/dl In ,, child who presents with jaundice. These are ethnicity, recent injections or
PLT 164 tr1nsfusions, contacts with jaundiced individuals, presence of dark urine or
Unconjugated bilirubin 294J1mol/l p1le stools, recent drug therapy, th~ ~eriod from onset of first sympto~ ~o
Conjugated bilirUbin · 0 JUOOl/1 11undice (incubation period hepahhs A: usually 2-6 weeks and hepatitls
Mother's blood group ORh+ve 1: 2-6 months), abdominal pain (hepatitis, stones), recent surgery (halotJ:lane.
Baby's blood group B Rh+ve toxicity) and family history (e.g. for Gilbert syndrome- unconjugated}.
·OCT Weakly positive
Blood .f ilm Numerous spherocytes seen
A 4-year-old child with recurrent episOdes of jaundice since birth
The most likely answer to this question is ABO incompatibility. Being with a normal examination
blood group 0 the mother has anti-A and anti-B antibodies and since the
Haematology normal
baby is blood group B this is a feasible explanation. There is also no Rhesus
Reticulocytes 1.8
incompatibility. Not all blood group _incompatibilities will result in
Unconjugated bilirubin 13~ol/l
haemolysis since in most cases the maternal antibodies are IgM and not
lgG and therefore will not cross the placenta. ABO incompatibility usually Conjugated bilirubin 67 ~mol/1
Urine: bilirubin +ve
produces a relatively mild jaundice and only very rarely is exchange trans·
Urobilinogen -ve
fusion required (cornpared with Rhesus haemolysis- see Table 6.2). Other
general features that would make haemolysis more likely is an increased This dearly demonstrates .a conjugated hyperbilirubinaemia. The answer is
reticulocyte count, ·reduced serum haptoglobin and a drop in the Hb Rotor syndrome. In paediatrics there are a number of conditions that produce
concentration. fiCU.rring or fluctuating levels of jaundice and they can be classified into two
NB A more detailed account of haemolytic disordeiS is found in Chapter 8 bin types:

A child ·w ho ~ a prodromal illness of 1-2 weeks and then llaemoJytic disorders


presents with jaundice lflemolytic disorders are ,..here .haem:>lyth. ~rises teP' . to occur as a result of
Unconjugated bilirubin 61~ol/l
~ogenous stressors such as ir.fection or exogenou., stressors such as drug
Conjuga~ bilirubin 42umol/l ldministration or surgery. Exampl~ of such haemolytic disorders are sickle
ALT 1949 international units/1 Udisease and G6PD deficiency.
AST HMl international units/1
ALP 310 international units /I a.herited disorders of bilirubin uptake, conjugation and excretion
GGT 489 international units /1 'these are Gilbert and Crigler- Najjar syndromes (unconjugated hyperbilirubi-
Urine: bilirubin +ve . aatmias), Dubin-Johnson and Rotor syndromes (co~jugated hyperbiliru-
Urobilinogen -ve ~lnaemias).

The most likely cause would be an infectious type of hepatitis. The commoh Gilbert syndrome: AD. 1-2% of population, bilirubin usually less than
est in the UK is hepatitis A, although also consider EBV and CMV as ~·I 35 ~mol/I. Diagnosis by exclusion of other causes. Biopsy is rarely neces-
bilities. Hepatitis 8 and C are blood borne and therefore these should be cuu Nry. Prognosis excellent. Defect decreased uptake and conjugation of
sidered if the history suggests such. bilirubin.
The hepatitis has produced hepatocellular damage as manifested b y tl Crigln--Najjar syndrome: Type I AR, Type n Ap. Very rare and presents in
raised ALT and AST. There is also an element of cholestasis as manifested I•~ the neonatal period with high levels of unconjugated hyperbilirubinaemia
the raised ALP and GGT levels. and can progress to kernicterus. Defect in type I: completely deficient
conjugating enzyme resulting in early death (orthotopic liver transplant
may be successful). Defect in type II: partial deficiency and may respond
to phototherapy and phenobarbital
"nable &.2 Comparison of ABO and Rhesus incompatibility Dubin-fohnson syndrome: AR. Rare. Conjugated hyperbilirubinaemia.
ABO incompatibility Direct Coombs' weakly -we Numerous spherocyte' Presents usually after puberty. Liver stained black by centTilobular
Rhesus incompatibility Direct Coombs' ~rongly -we No sph6o<ytes
.1 46 melanin. Late rise in bromosulphthalein (SSP) elimination curve at 90 min 147
but normal at -15 min. Abnormal choiecystogram. Defect: d<.><:reased hepatic disease and ulcerative colitis
excretion of bilirubin.
I um studies are the radiological investigations of choice.
- &>lcJr syu.lrollut: AR. Ran~. Conjugated hy~rbilirubinaemia . Presents at a
_.. d' . tr'ctures 'rose thorn' ulcers, 'cobblestone' mucosal appear-
younger age. liver biopsy normal. Raised BSP at 45 min and no secondary ,.11.,n 1sense. s 1 •cosal oedema) and skip lestons.
· An t of the
y par
rise at 90 min. Normal oral cholecystogram. Defect unknown.
ICt (seconda~ to ~ubut most commonly it involves the small bowel and
lowel may be ~volv 1 d follow-through is the investigation of choice.
lhftefore a banum mea an
Neonaul hepatitis 8 immunisation
-~ This is a common question in the exam and relates to the protocol for immu-
t""'atiw colitis: This will only affect the colon ~ a co~tin~ous /a~hl:on
........g distally Thus a barium enema will be the uwestigation o c otce.
~ nisation of babies bom to mothers who are hepatitis 8 surface antigen p osi- _.... · . th 1
Ius' findings are: shortemng of e co on an
d loss of the haustra pro-
. . 'l
:::::.1
t/)
t in-. It is essential to know the serology of the mother. ~~~the 'drain-pipe' cOlOn (also backwash ileitiS With temunall ~Um
We can divide the n1other who is hepB SAg +ve into three main types
< Jt>t•o:nding on her serology:
lftVOlvement rarely).

E 1. Higll infectit•ity: 'e' Ag and no 'e' antibodies. Risk of baby being hepB 'sing enterocolitis
C'G
>< SAg +ve is SOO/u.
ere four classic features that may be present: (1) fixed oede.~tous _loo~~
w :!. lntaml!diatt• i"fectit•ity: ~o 'e' markers.

-(,)
'i:
.!!1
"0
Q)
C'G
3. Low iHfrc:tit•ity: 'e' antibodies and no 'e' Ag. Risk of baby being hepB
SAg +ve is 10°/c,.
In the first two cases it is recommended that active immunisation and passive
immunisation be given into different thighs. ln the third case of low infectiv-
. . k
Mwel w1th thtc ene wa '
d ll· (2) intramural gas - pneumatosiS mtestinahs,
. . ·
I file air in the peritoneal cavity tf there IS a perforation prese
1film); (4) gas in the biliary tree.
nt (ask for a

0. inal obstruction
ity it is recommended to give just the active immunisation. In all cases it is
advised that passive or active immunisation takes place· within the first 12 h . films are portant Generally there may be ,gas-filled dis-
un·

1and supme · . R be th
of the baby's life. The acti\'e vaccine doses are repeated at 1 and 6 months and ~ t· . f bowel with multiple horizontal flwd levels. emem r e
seroconversion tested at 1 year of life. If negative then a repeated booster o( _ . oops o di 'call Small bowel have
lllren between small and 1arge bowel ra o 1ogt y.
active vaccine is given. A booster is given at 5 year-- ">f age. ,tile a::lares which completely cross the lumen and occupy a central por-
The importance of neonatal immunisation is to reduce the risk of cirrhosis of the abdomen and large bowel have haustra that do not compl~tely
and hepatoma in later life. · the lumen and occupy the outer portion of the abdomen. often Wlth a

rGASTROENTEROLOGY RADIOLOGY·,,·.· .. -,;.:.. . · ·t:. ;'J


When looking at an X-ray of the abdomen be sure to have it the right way around sception
If the gastric bubble still appears to be on the right and Liver shadow on the leh lafacteristically on a plain film there is a lack of gas in the right ~c fossa
then this may represent situs in versus. Ask to see a CXR to look for dextrocardin features of small bowel obstruction. Barium enema ccu:
~ both dtagnos-
. · bnn·aing about reduction. Charactenstically shows the
1nd therapeutic m o-· . kn ckl f
A - the barium moves proxunally a u e o
Hypertrophic pyloric stenosis liled spnng
• ,
appearance. n.:. . . f
~cting bowel can be seen. Ultrasound shows a mass wh1ch lS made up o
A plain X-ray may show absence of air distal to the pylorus. It is usually
.-centric layers.
demonstrated well on barium meal: a normal gastric outline followed by a l'lilf
row. elongated pyloric channel referred to as the 'string sign', delayed gastrh
emptying and 'mushroom' appearance of the duodenal cap. Ultrasound demon• ••~SPrung disease
strates a thickened pylorus and is often diagnostic with a typical history. M!etnt gas in the ~lvis on a plain abdontinal radiograph ~f' ~e abdo~en in
1111 rone ition s~!'lg!y suggests the diagnosis. A banum enema IS best
Duodenal atresia p pos ~ ~~ colon (that is' no prior enemas). It may demonstrate

Because of the distension of the first part of the duodenum this gives the cha1
acteristic a ppearance of the 'double bubble' with the larger gastric bubbl
t on an unpre-;:o--•t:U . .
transition 7_.· .1e between ganglionic and aganglioruc ~ents.
This ·
...&.. ct · •. c 'ice cream cone' appearance at the transition zone, as the
V1Dra er...I I d'
gtves
t . class'cally
1
..,glion~.: section is tonically contracted and the recta 1ame er lS
148 (left) adjacent to a smaller duodenal bubble (right}. 149
Mrrov · ~r than the sigmoid diameter.
Volvulus J!tlore produce some confusion. These include: pneumonia (especially
. • , . . . lower lobe), pharyngitis (especially streptococcal}, pyelonephritis,
This can cause a corkscrew appearance wtth other features of mtestm
. b ) . neph rotic
co1tc, . syn
· d rome, penca
· rd't'
1 ts,
h aemo1y ti'c cnsts
· · (sueh as
obstruction (see a ove . cnsts , rmgrame am11y tstory or tstory o recurren t abdomma
. . ) . . (f . h' h' f · 1
Q)
), infectious mononucleosis (hepatic or splenic origin), hypoglycaemia,
·-
"C
Meconium ileus
. .
mellitus (especially ketoacidosis), hypokalaemia, porphyria and
poisoning.
. -ns
There is characteristic bubbling (ground glass appearance) in the meconiu
> plug with the other features of obstruction proximal to it. There may be a
·~ associated distal microcolon seen in contrast studies. .......trt abdominal pain
:I
U) a common clinical presentation in children. Ninety per cent of cases
c( G1 perforation organic cause. A diagnosis of 'the syndrome -of abdominal migraine'
This will produce air under the diaphragm if the child is erect and there mal~,,. in a child who is thriving, with periumbilical pain (remember the fur-
E
ns be delineation of the falciform ligament. pain is from the umbilicus the more likely pathology is present -
)( law). There may be recurrent nausea and vomiting and a positive
w history of migraine or recurrent abdominal pain. The episodes are usu-

-0
·;::
.~
"C
Q)
ns
Paralytic ileus
Gas is distributed diffusely throughout the bowel.
long or severe and may be triggered by certain situations. Irritable
syndrome is being increasingly diagnosed and is suggested by a histo ry
llll!ll=~nt abdominal pain, bloating, alternating diarrhoea and constipation
in children who are described as 'worriers'. Minimal investigations
c.. Opacities on the X-ray include FBC, ESR, AXR and urine for MC&S.
This is divided up into the various possibilities.
- Intestine: foreigrt body, meconium peritonitis, TB \)a in w.ith hyponatTaemia
-Peritoneum: speckled peritoneal calcification caused by bowel oelrforatliullillllio. are m any questions that present a case of a child with abdominal pain
meconium ileus antenatally biochemistry picture of hyponatraemia. You must know the differential
-Liver: gallstones, TB, haemangioma, hydatid cyst/amoebic cyst which includes the following possibilities:
- Kiduey: renal stones, nephrocalcinosis (remember hyperparathyroidism)
-Bladder: stones, foreign body, sc.h istosomiasis
-Tumours: Wtlm, neuroblastoma
- AbdominDI wall: post surgery in scar tissue or calcified haematoma.
~
Especially ketoacidosis. Look for o ther clues in the biochemistry
Microcolon
This is usually a slide of a barium enema with a section of very narrow disease: There may be other signs of hypotension and shock. The
It Is associated with Hirschsprung disease, meconium ileus and a left mh .....,..u ... will usually be ra ised.
colon which is associated with the infant of a diabetic mother. ,. ..,_.,., intermittent porpllyriJl: Abdominal pain is common during attacks and
occurs secondary to SIADH caused by hypothalamic
Anorectal·. atresia - N"'"""''.,"''" There may be dark uriu..e and neurolngical features.
Contrast X-rays of a fistu la between rectum and bladder/urethra/ cause for the abdominal pain" and hyponatraemia.
or of a radio-opaque anal marker failing to reach the air bubble ln secondary to diarrhoea and vomitirig.
rectum.
pain with neurologicai features
useful pattern to be familiar with in the examination and in clinical
In paediatrics there are a number of diseases that can present w ith abd is the combination of abdominal pain and neurological features. Here
·150 inal pain that do not d e rive from the gastrointestinal system and diagnosis includes: 1S1
- ~nd poisoning (an exam favourite). TIUs produces abdominal featur f ll bladder, bowel, kidney .or tu.mour. Remember that. the ki~ney ~y be
(abdominal pain, vomiting and constipation) as w e ll as neurological fe iatructed and therefore glVe ~ to a. culture-negative urme spec1men
ne'""
tures such as signs caused by raised intracranial pressure, seizures, sixth pite the presence of an abscess m the kidney. Perform an ultrasound scan
palsy, ataxia and peripheral neuropathy (mainly motor). Neurological ~ .nsider IVU or DMSA scan if considering renal origin).
CD tures result from cerebral oedema, vasculitis and increased capillary pel'lllt
"C ability. In addition there may also be a microcytic hypochromic anaem
::'1 ~emolytic anaemia and basophilic stippling. Fanconi syndrome may oo
(!)
and b~ad lines may be seen radiologically (grow_th arrest lines at the metap~ the history is one of several weeks to months of general malaise, anQrexia,
C'CS ysis of long bones). Test the urine for Fanconi type picture (glycosuria, ph<a ght loss and any GI symptoms then always conSider tuberculosis in the
> phaturia and so on). There is an increased urinary coproporphyrin, incre erential diagnosis especially if the patient is Asian or· immunocompro-
·~ . In addition there may be an abdominal mass, hepatosplenomegaly
::'1 .delta aminolaevulinic acid and normal porphobilinogen. Note that sometin
U) there is a. clue in the question: for example, if the child lives in an old ho ascites.
c( (walls often painted with lead-<ontaining paint).
E -Acute intermittent porphyria (dealt with in Chapter 10): During attacks 1 arge from the umbilicus
C'CS
>< can produce abdominal pain, vomiting, constipation and dark url1
Neurological features may include personality changes and varying neu~
m
ls may be seen a number of conditions. You should be aware of the dif-
w t possibilities: These include: (a) umbilical sepsis; (b) patent urachus -

-CJ
'i:
."C~
CD
C'CS
logical problems ranging from mild peripheral neuropathy to quadripiCJ frtne discharge from bladder; (c) patent vitello-intestinal duct- faecal dis-
and respiratory failure (caused by neurona l damage and demyelinatio ~e; (d) umbilical granuloma (see embryology notes earlier in chapter).
In order to differentiate it from lead po'wning (during attacks) there b
increased urinary delta aminolaevulinic acid and raised urinary porpl
bilinogen.
D.
-Sickle cell crisis may well have combined abdominal pain and neurologl \'ou may b~ shown a slide of an omphalocoele or gastroschisis. In an
features (usually with a preceding characteristic history in an approptl t~nphalO<:Oele abdominal contents are herniated into ~ sac comprising
racial setting). IIMion and peritoneum (as a result of deficiency of the umbilical ring). The
IIJrlbilical cord is attached to the vertex of the sac (exomphalos minor contains
- Hypoglycaemia.
pt and exomphalos major - larger defect - contains gut and liver). It is asso-
- Wilson disease (see later). llated with Beckwith-Wiedemann syndrome, cardiac defects (e.g. tetralogy of
rauot), imperforate anus and trisomies 13 and 18. In gastroschisis the small
Abetalipoproteinaemia ltowel herniates through a defect which is found to the right of the umbilical
/Pfd because of a defect in the anterior abdominal wall. There is no peritoneal
Think of the rare AR disorder of abetalipoproteinaemia in a child who pr~ lOVering. The exposed bowel is at risk of infarction. .
with diarrhoea or steatorrhoea and progressive neurological features with a 1 Complications of both include heavy losses of protein and fluid as well as
gressive a taxia, neuromuscular d egeneration and retinitis p igmentosa (nc t loss and infection. Initially occlusive film iS placed over the hemial sac
logical features seen after the age of approximately 10 years). A blood film tt d free drainage of gastric contents is performed in order to prevent gut dis--
show acanthocytosis (erythrocyte$ with spiny projections from the surface -
ion. Intravenous fluids and plasma are given, monitoring haemodynamic
also post splenectomy). Typically there is no post-prandial lipaemia. Rcllr
tus and urine output. ·
pigmentosa and acanthocytosis are thought to be secondary to vitamin E
A closure is then performed (usually in two stages). Complications of
ciency. It is caused by defect in apoprotein B production by the intestine wl
ming the bowel into the abdomen include bowel infarction and occlusion
leads to defective Lpl, VLDLand chylomicron synthesis and thus failure of11
o1 the inferior vena cava.
transportation from the intestine or liver {including malabsorption of fat aJ1d
soluble vitamins A, D, E and I<). Other features include very low levels o( r
lesterol and triglycerides and the consequences of vitamin A, E and K defid
Treat with medium-<:hain triglyc~des and fat-5<>luble vitamins.
" a Caucasian child who presents with a Coombs' negative haemolytic
lnaemia and splenomegaly ~en consider hereditary spherocytosis (AD). In
Pus collection
lbout 20% of cases of hereditary spherocytosis splenomegaly will be absent.
With any clinical history where there is a swinging temperature wlth There may be a history of neonatal jaundice in about half the cases. Diagnosis
T52 abdominal mass you must think of a pus collection which may be in the II It usually made on blood film. Remember that the red cell fragility test iS not ~153
!Enterobius vermicularis - nocturnal itching prominet:'t} is causing the problem.
reliable until about 6 months of age. These patients may come to clinicians in
aplastic crisis (like sicklers) if infected with the human erythrovirus (former-
You would carry out a detailed history and examination and test for thread-
ly parvovirus) type IH9 (see Chapter 8).
worms with the Sellotape test (where eggs can be identified microscopically).
Although as paediatricians you should have a high index of suspicion of
In some questions use is made of the connection of a child who has a
haemolytic disorder (e.g. hereditary spherocytosis) and develops recurrent
lbuse this question is really seeing whether you have a sensible and discrim-
abdominal pain. In addition to haemolytic crises (especially sicklers) think of lftltory approach to your patients.
the formation of pigment gallstones producing biliary colic, acute and chronic
cholecystitis and perform an ultrasound scan to confirm. Necnrtising enterocolitis
4 question dealing with a premature baby who develops abdominal disten-
Anaemia---and abdominal pain Un, bile-stained v9miting or bloody stools should immediately suggest to
• the possibility (;f necrotising enterocolitis. However in the .exam the pres-
In a child presenting with anaemia and abdominal pain you must not forget
Illation may not be so obVious.'There may be non-specific signs such-as vom-
the potential sites of bleeding in the gastrointestinal tract. These may present
as haematemesis, melaena, frank blood PR or in occult loss so that the symp-
tdng, hypotension, thrombocytopenia, temp~rature instability, apnoeas and
llehargy. The babies have almost always been fed. There may also be an ante-
toms and signs of anaemia predominate. Know vour lists of causes of Gl
bleeding, many of which lead to painless loss of blood: oesophagitis, swal-
Uta! Doppler report of reversed end-diastolic flow (associated with NEC).
lowed maternal blood at birth or through cracked nipples (these last two a ICI\ow your investigation and management.
cause of rectal bleeding in neon.-'ltes), Mallory-Weiss tear/syndrome, gastritis,
peptic ulcer, Meckel1s diverticulum (diagnose with a technetium isotope scan Ctohn disease
which is taken up by gastric mucosa), inflammatory bowel disease, foreign
body, haemangioma, bacterial gastroenteritis {especially Snlnronellll, EHEC, £. teenage child w ho presents with an insidious onset 9f weight loss,
coli, Cnmpylobncter, Shigella and Yersinia), intussusception, NEC (in neonates),Udominal pain, unexplained fever and possibly diarrhoea should alert you
volvulus, polyps, cow's milk protein intolerance, vasculitis (e.g. HSP), anal • the possi~ility of Crohn disease, which is on the increase in children.
fissure, sexual abuse and coagulopathies. Indeed the failure to thrive may well precede any· gastrointestinal symp-
eoD\5. There may be a right iliac fossa mass. It may present as an acute ileitis
fllembling acute appendicitis. Anal lesions (skin tags, fissures and fistulas)
GOR common. In the exam, questions will of course make use of the huge
In a baby who preSEnts with persistent vomiting you should know the differ lllnge of extraintestinal features common to the condition: delayed puberty,
entia! diagnosis whlch is available in most paediatric texts. Don't forget thl• lllort stature (these two are a common accompaniment to most chronic
huge range of possibilities ranging from rais~d intracranial pressure through Wlammatory conditions); clubbing, arthritis - 20% have joint involvement
to a metabolic disor:ler. Your investigations will be directed hom the history presentation and it is usually mild, asymmetrical and migrating, resolv-
and examination. For exa~ple a common cause of persisting vomiting in n lla without deformity, usually involving lower limb joints. Arthritis may
de Gl symptoms. In addition aphthous ulcers; angular cheilitis, ery-
3-month-old baby who may have an element of failure to thrive is gastro-
oesophageal reflux IGOR). Remember another common presentation of COR
which is coughing and possibly apnoea, especially shortly after feeds. Your
investigations of ch~i~~ will therefore be a pH probe study and barium swal -
E a nodosum, uveitis, episcleritis, <:onjunctivitis and also occasionally
urrent liver involvement (chronic active hepatitis, gaJlstones and bil-
cirrhoSis) may occur. UlCerative colitis (UC} shares many non-GI man-
lllltations ~ith Crohn an d clinically can be difficult to distinguish from it.
low. However a baby who is vomiting and has a head circumference that ~
increasing dispropationately to the rest of the body will need a cranial sca11 llowever rectal bleeding (often bloody diarrhoea), mucus passed rectally
etc. Thus your histay and examination will direc~_your evaluation. IKI abdominal pain (lower abdomen) are usually commoner features in
UC. A formed stool implies rectal disease and diarrhoea ImplieS more
ll&ensive disease. lnvestigation of choice for UC is colonoscopy and biopsy,
Bruising around labia majora and anus I'd barium follow-through for Crohn.
A not uncommon finding .o f bruising around the labia majora and anu•
including excoriati<J'\ and erythema, does not necessarily cause conc~m about ~sulcers
sexual abuse (altho11gh this should a lways be considered in such cases). Thl
is esp~all~ so when the~ is n? invo~vement of the labia minora or the vagi 4 question may present a child with recurr~nt aphthous' ulcers (or aphthous
nal orifice 1tself. Th~ leadmg dtagnos1s would indicate that some sort of itrl ltiDmatitis). Most are idiopathic but may be associated with Crohn disease,
154 tation such as alleJgy to washing detergent, for example, or threadworm Wftrative colitis and occasionally in coeliac disease, Behc;et disease and neu- 155
+
Q)
'0
tropenia. Beh~t disease has three main features consisting of recurrent
painful oral and genital ulceration (scrotum, penis and tabia) often the pre-
senting feature, ocular inflammatory disease (pain, iritis, posterior uveitis}
and neurological involvement including aseptic meningoencephalitis,
pseudotumour cerebri and severe brainstem and cord lesions.
Gas trointestinal symptoms may also occur and are varied. Lesions resem-
your differential diagnosis of obstruction. Treatment often ends up being sur-
feaL

Pllotitis
;:, bling erythema nodosum may occur. A medium-large sized joint arthritis Ocxasionally there are questions about parotitis in children. The commonest
(!)
-> may be seen. A migratory vasculitis (thrombophlebitis) may occur. Males are •use is mumps which has a 2-3-week incubation period. Check the MMR
llllmunisation status. It most commonly affects the parotid glands bt,1t sub-
fCS twice as commonly affected as females. HLA-BS associated. The pathergy test
involves a sterile subcutaneous puncture (e.g. a blood test), which in Beh~et Nndibular glands may also be affected. Acute suppurative parotitis is most
·~ cammonly caused by Staph. aureus and StrqJ. pyogmes and occurs in debilitat-
;:, may give rise to a bullous/pustular reaction within a couple of days. It usu-
en . ally has a benign relapsing and remitting course. ed patients who are dehydrated. Acute sialadenitis (more commonly affecting
<( lht submandibular gland in about 80% of cases) is caused by a duct calculu!>.
Increasingly, recurrent· parotitis is being seen in HIV infection. Recurrent
E "Toddl~s diarrhoea•
ICUte inflammation may be seen in children without stones or strictures and
fCS
>< A child who is thriving and well nourished but presents to the clinician with IIIUally improves with time (recurrent p arotitis of childhood). It produces a
w chronic diarrhoea with no obvious cause given in the question leads one to plinful parotid gland (unilateral or bilateral) with erythema around Stensen's

I I -0
'i:
.!2
'0
Q)
fCS
consider 'toddler's diarrhoea' as the diagnosis. Key points in the history that
you should look for are the typical age, that is, 6-24 months; parents often
report seeing particles of undigested food in the s tools; and the absence ol
failure to thrive. Management is reassurance and it usually resolves sponta·
duct (or occasionally pus discharging from the duct). Chronic parotitis may
Ill a r-eSult of salivary duct dilatation (sialectasis) resulting in recurrent infec-
llan. SjOgren syndrome is an ·autoimmu.rre disorder that" principally affects the
llllvary and laaimal glands causing dry eyes and dry mouth. One-third of
a.. neously at 2- 3 years (obviously in the clinic additional investigations such as tients have chronically enlarged slightly tender parotid glands.
a stool sample would be also carried out). C ~estigations for parotitis would include X-ray for stones, MC&:S of the
llpressed pus from Stenson'~ duct, sialograms of the glands and possibly an
Pseudomembranous colitis H1V test. .
This is a potential case in the exam. It ·is caused by an alteration in the nonnal
balance in gut flora by antibiotic therapy with res ulting overgrowth ol hlvic appendix abscess
Clostridium difficile (it is the A and B toxins of CL difficile that are pathogenic} Aquestion that you should ~ognise is the child who may have symptoms of
Children present with varying degrees of symptoms ranging from mild . pendicitis that may settle and then recur with the patient in urinary reten-
' '11\!atery diarrhoea with crampy abdominal pain to severe watery / bloody diat IDn (usually with a palpable bladder). The cause is a pelvic appendix abscess
rhoea with a high feve r, raised white cell count and even toxic megacolon and ~ often causes urinary retention.
p erforatiol). It is most commonly associated with the use of dindamycin
ampicillin, penicillins and cephalosporins.
Symptoms may begin during the course of antibiotic treatment or up to i with melaena or haematemesis
weeks following the course. Sigmoidoscopy reveals the characteristic yello11 case may describe a child with cystic fibrosis who presents to the casualty
necrotic areas on the mucosal surface. Stool culture for 0. diffici1e or assays f01 artment with m elaena or haemat'emesis. The causes of such a gastroin-
its toxin can be carried out. It is less reliable for infants and neonates, m any rl tinal haemorrhage include: (a) portal hypertension having given rise to
whom commonly carry both the organism and the toxin in their bowtl hageal varices with their subsequent rupture; (b) reduced fat-soluble
Treatment consists of oral vancomycin and metronidazole. min absorption and thus reduced vitamin K absorption with consequent
ltficiency of clotting factor synthesis; (c) liver involvement in cystic fibrosis
Bezoars y affect clotting factor synthesis; (d) in a child it may sometimes be diffi-
lllt to distinguish between haematemesis and haemoptysis; (e) hyper-
You may come across bezoars in the exam. They are collections of indigestib~ iplenism secondary to portal hyperte.n sion causing thrombocytopenia.
swallowed material in the gut, most often seen in the stomach. They may I•
made up of undigested milk proteins or hair collections (seen in trichotilh•
mania, often in adolescent girls and possibly psychiatric disturbance). n. liac disease
156 importance of bezoars is ·that they may result in obstruction. Keep them ~ ltauure to thrive after o nset of weaning (thin, muscle wasting especially but-
tDclc wasting, hypotonic and pale), diarrhoea (soft, pale and sticky) and 151
ause of invasion of IVC}, hepatoblastoma which is associated with an
abdominal bloating should alert you to the possibility of coelia~ disease. .sed platelet count and increased alphafetoprotein, increased bHCG (the
Oedema, rickets, iron deficiency anaemia may also occur and th~ chtldren are nwo tumours are associated ·with Beckwith- Wiedemann syndrome) and
oftl!n depres~d c\nd irrit.1blc. . ftlblastoma. All these can present with an abdominal mass. An IVP of a
Onset is usually by 2 years of age and symptoms usually start at the mtro- lastoma reveals a filling defect which distorts the calyceal system, dis-

-
Q
duction of cereals at 5-6 months of age. You may be shown a growth chart of the kidney and does not cross the midline. The IVP in neuroblastoma I»
· a child where the weight begins falling and crossing centiles from the age _of y cause displacement of the kidney with little distortion of the calyceal sys- fA
gluten introduction. Vomiting is more common ~e ~arli~r the onset of~ dt: tince it is extrarenal (usually adrenal gland). cr scan will also differenti- 0
co
ease. It is associated with HLA-B8. Late complications mclude gas~mtesti­ lhe two since one is extrarenal and the other intra renal (see Chapter 4 for ::::s
nally!pphoma (heralded by a wotsening in cl_inical state), myopathi~, neu- details). ~
ropathies, hypospler.ism and later in lif~ gastnc and oesophageal caronoma. "''
0
Don't forget the associc\tion with dermatitis herpeti.formis. • • . 0
A typical slide question might show a miserable chi~d wi~ ~·as~ ~u~- panaeatitis cc
tocks and a bloated abdomen. An important differential dtagnos~ ts p~chasts fhlt Is rare in children but may tum up in a question. Symptoms include severe
'<
which can present with bloating, flatulence, diarrhoea, abdommal pam and !Woaunal pain radiating to the back with shock and tachycardia. The main
malabsorption with stt!atorrhoea and failure to thrive. It is investig~ted by - i n children include trauma, drugs, viral illness, mumps, hyperlipidaemia,
repeat stool microscopy (since Giardia is excreted at inter;rals), look~g for P*d hyperparathyroidism. Look for a raised amylase in the biochemistry.
cysts or trophozoites or duodenal aspiration. Treatment is w1~ ~etro~tda~ole
which is sometimes given empirically on suspicion only.lnitial.nvestiganons .........__ •
in coeliac disease would include antibodies (IgA antigliadin, antiendomysial ~prung dtsease
and anti reticulin antibodies- remember however that 3% of coeliacs have IgA fNa can present in a number of ways. Most commonly it is seen in males (M:F
ddiciency), jejunal biopsy (see before), examination of jejunal mucosa and • 4:1): (a) delay ·in passing meconium in first 24 h (90%}; (b) intermittent
jejunal aspirate for Ginrdin. . tMt'l obstruction or chronic constipation; (c) failure to thrive; (d) a severe ente-
Other differentials include cow's milk prote~ intoler~ce which causes (coinmoneJ;' ~~nates) may perforate the bOwel (and may occur even
vomiting, diarrhoea (occasionally with blood), failure to thrtve, _rash, wheeze llpair). Most cases (90-95%) of Hirschsprung present in the first year of life
and eczema. Treatment o f coeliac disease is with a gluten-free dlet (no wheat, of these in the first month) but may present later. There can be short seg-
barley or rye but maize and rice products may be eaten). or more extenSive involvement. The anal canal and rectum are usually free
llllees and the examiner may feel a tight grip on the examining finger (see ear-
Mediterranean fever atDtes on radiology}. A rectal biopsy under sigmoidoscopy may identify
of ganglion cells, and staining for acetylcholinesterase reveals abner-
Recurrent episodes of fever with abdominal pain in a child of Mediterranean prominent nerve fibres (a possible slide question). Also perform mano-
origin (e.g. Sephardic Jews, Turks and Arabs) should lead you to suspect studies on the rectum. Th~ internal anal sphincter is always involved and
familial Mediterranean fever. It is a disorder of polymorphonuclear cell~ proximally a variable distance.
Attacks usually start between 5 and 15 years but this is not a_lways the ~ tment of neonatal Hirschsprung consists of producing a aefunctioning
Attacks consisting of fevers (over 38SC) with se~i~ (ma~y. abdonunnl-atomy, removing the aganglionic segment and then pull-through repair at a
pain with tenderness, but also pleuritic pain, large JOmt arthotis and perl . Another anatomical abnormality that may be associated with constipa-
carditis rarely) occur approximately monthly for a few days, but the frequ~n W!udes an anteriorly located anus where the anal canal and external sphinc-
cy decreases with age. Skin lesions such as erysi~las may occur. A famtl~ • anteriorly placed. In anterior ectopic anus the extemaJ sphincter is in the
history may be present in half the cases. The question may have presen~d • position but the anal canal and internal sphincter are anterior (this can be
child with·a recur'rent acute abdomen having been operated on several timt• a shelf projection on PR examination). Anal fissures may also cause consti-
with no pathological finding. wee and ESRare raised dur~g attacks but 0~ 1 as a result of pain and inhibition behaviour. Remember that any cause of
mal in between. Genetic testing for the commonest mutations can be carncul mnstipationmaycausesoiling.Fluidfaecespassaround the hard impact-
out. Treatment is with colchidne. A serious complication is amylokl~>~lt 1mass since the distended rectum fails to control the bowel motion.
(mainly vascular involvement).

'I• ..,Niltt episodes of vomiting


Abdominal tumours
can be bile-stained and occur with abdominal pain, both of which may
Know about the commoner abdominal tumours in infancy which inclUil• spontaneously and can be caused by recurrent volvulus which is most 159
l5S nephroblastoma (can ha\·e ha~maturia and rarely cause tricuspid regurgitath~
commonlv a result of malrotation. Can also be because of duplication cy~ts or lnovement disorder (tremor, rigidity); (d) haemolytic anaemia; (e) Fanconi
ladd's b.;nds (see notes on malrotation earlier in chapter). •~rome; (f)becataract (sunflower type).
,ou may asked for your inves.tions to ronfinn. These are: low serum
•aendoplasmin (also seen in nephrotic syndrome, malabsorption and protein-
Protein-losing enteropathy bing enteropathy), high urinaJy OlJ'Pe'l" exc:retion increasing with penic:il-
. . . . . . !.mine challenge, slit-lamp examination ol the ..,_ for detection of
. . .
count one has to cons.a der a protean-losmg enteropathy.
- .. .
In a question that presents a child wath chrome daarrhoea and a low prote111 .,_yser 1::'1....:--&.- •
-~ =·~ n•:.- nngs
(dull fan~A -•-.........a
~ lhP. cornea -'---L ~..........;,..). A _:_._a
ula-
J -d

lev .
.
green t~o~'"'-'AUU•cu gran r epostt at the
.
lim
.
bus
.- - ......._ pau""b'_......... acu::ocu copper e1 Ill a liver b10psy
1. Exudation from ulcerated mucosa, for example intestinal TB. epeamen. Also screen siblings (AR). Treat with ~e. Pathology: fail-
2. Defective lymphatic drainage, for example intestinal lymphangiectasia. Ill of liver to excrete ooppec into bile so that aa:umulation cause:; suppressed
NB Look also for low Ig levels and very lo~ lymphocyte count with a ..-uloplasmin levels and exass ropper spills out ol the liver into the circula-
normal remainder of the wee. llan and deposits in various tissues causing the~ pathology.
3. Others include coeliac disease, food allergy and CF.
Alpha-1 artitrypsin deficienq
Coma and hepatic dysfunction Hepatomegaly and a prolonged neonatal oonjugated hyperbilirubinaemia is
A pattern that comes up in questions and you should be familiar with is til! I ~ ~ pattern and you should know the differential diagnosis
child who pi:esents with: (1) coma or near coma; (2) hepatic dysfunctiol IIWtn ~rber an the cha~ A ..are condition but relatively common in the
Apart from hepatic failure and concurrent encephalopathy be familiar wlP ~ ~ alp~-l.antitrypsin deficiency. It is important to know the different
the other causes. "'YS m whlch tt can present.. lbe commonest is in adults with premature
1he list includes Reye syndrome: suspect this in any question where a chi ~ ~ b~ (not seen before lhe fust decade). Less commonly
develops an acute onset of encephalopathy associated with hepatic dysfuncti~ Ipesent:s 10 infancy Wlth neonatal cholestasis (a cause of prolonged neona-

Peaks al 5-6 years of age. Usually a biphasic illness with a viral URTI follow II Ja~u:e), ~tomegaty, cirrhosis and liver failure and there is a longer
{lbout 5-6 days later by intractable vomiting. This is associated with confusl lam risk of he~atic carcinoma. Eighty-five per c:e:nt are asvmotomatic.
agitation and a deepening level of unconsciousneSs (the result o_f raised intra Jn 1be question you~ usually directed to it being the mOst- jj..j(eiy diagno-
nial pre:sSun;!)· There is no jaundice, no fever and the liver may be enlarged. • after other metabolic screens are negative, ladioisotope labelling tests are
Investigations: bili - normal, ~ - raised, PT time - increased, ~ ":"d ~ ul~ scan foe a choledochal cyst (which presents with
caemia in approximately 15%. Unlglown aetiology but associated le JCiundice) 1S negative. Smce AlAT enzyme is an acute phase reactant
f!Denwphilus influen::.ae A, B, varicella and the administration of aspirin in ~:t ma~ be artificla.J!Y ~~ to no:ma~ levels in inflammatory disorders.
dren under 12 years. Histology - a possible slide question - shows fatty t~re .p1 ~rotease inhibitor) typing 1S pedomted. Genes express co-
mutation with no necrosis or inflammation and swollen mitochondria in ~t inhentance.lnfants with the ZZ phenotype are at risk of neonatal
liver and other tissues. fllpatitis and later in life of lung disease The MM phenotype is normal and
Treatment is supportive including treatment of hepatic failure and hete~en~us MZ phenotype may cx may not have hepatic disease.
restriction. Other differential diagnoses to exclude are: (a) fatty acid tment 15 a liver transplant whi<h cnnverts lhe n!Cipient to the Pi pheno-
amino acid and mitochondrial electron transfer defects; (b) urea cycle of the donoc.
(more likely in infants); (c) salicylate and carbon tetrachloride pqisoning.
sepsis and (e) hypothermia.

Wilson disease
A rare syndrome but very common exam topic is Wilson disease and
ing the related questions requires recognising the classic presentati011
terns. These include: (a) presentation usually after 8 or 9 years of as•
chronic liver disease, which may present with hepatosplenomegaly, cirri~
jaundice, hepatitis and I or fulminant hepatic failure (liver disease IN•
absent at disease presentation); (c) neurological featureS may ·be 'the fir!ll
entation and include intellectual impairment/behavioural change
160 often in questions as reduced school performance) and ...,.,.,,.,...,.......
shows perilobular fibrosis with excessive iron deposition. Trea_~ent is
hernia (Afro-Caribbean, Down, hypothyroidism, mucopolysaccharidoses and
prematurity).
with repeated venesection. A secondary form of haemochromat.osiS IS seen
in children needin~ r~peated blood transfusions. for example tn beta tha- -Take both hands and iriSpect both palmar aspects and the nails. Look par-
lassa~mia major (see Chapter 8). ticularly for palmar erythema, anaemia (nail bed and palmar creases),
dubbing (know the causes) and koilonychia (iron deficiency).
Q)

·-
"0 Chronic active hepatitis - Look at the eyes. Inspect the sclera for jaundice and the conjunctivae for
anaemia. Although uncommon clinically, look for Kayser- Fleischer rings
In a girl (usually over 6-7 years of age) who presents with an iriSidio~ onset seen in Wilson disease (not uncommon in exam short cases).
-; of jaundice, general malaise (including weight loss and _ano~a) and
> hepatosplenomegaly consider chronic active hepatitis wh1c~ 1S • usuall! -Inspect the mouth. Perioral pigmentation in Peutz-Jeghers syndrome.
·~ autoimmune. Test for nuclear autoantibodies, smooth muscle antibodtes, anti· Look for aphthous ulcers. Ask the patient to stick out his tongue.
::s lin~r microsomal antibodies. Treatment is with steroids : azathioprine. F:M Macroglossia is as~iated with hypothyroidism, Beckwith-Wiedemann
C/)
ratio 3:1. Prognosis: 70"'<> are normal at 5 years post therapy and the re~in­ syndrome and the mucopolysaccharidoses. In Down syndrome the
ct:
.. ing 30"u de,·elop cirrhosis and lh·er failure. Pathology demonstrates piece- tongue protrudes secondary to hypotonia but is not enlarged. Look at the
E meal nec rosis.
dentition.
C'CS
>< - Ask the patient to sit forwards and with both hands gently palpate the cer-
w vicallymph nodes from behind.
0
'i: This is a commonly assessed system in the short cases and you should havC' -Having inspected the abdomen fully before (after general inspection) you
:! a good, reproducible and effective system. For the sake of simplicity th~ din• now palpate the abdomen. It is absolutely essential that you look at the
"C
Q) ical section also incorporates the examination of the rena' syste~ (as 1t doea child's face during palpation since any discomfort elicited will usually be
C'CS clinicaUy) in order to save on repetition in the renal chapter. As mother sys obvious and you can adjust your palpation accordingly (a scream from the
D..
terns (if you are given a choice) I advise you to exaniine the syst~ fully child in pain as a result of your·examination does not impress the examiner
before presenting your findings to the examiner rather than presenting 111 and <:ould· fail you). In .addition it also shows that vou are a sensitive doc-
you examine. It appears more professional and you are less likely to mak lor. The examiners will be looking for this caring and gentle ~pproach
blunders. ~ughout the clinical examination. In fact this may be a good time to
First, introduce yourself to the patient/parent. Then expose the abdom\!11 mteract and ~tract the child (obviously depending on the age- for example,
from the n ipples to the knees keeping the child's pants on and generally 'So let's see if I can feel what you had for breakfast'). Don't forget that the
maintaining the dignity of the patient with a blanket (if available). examiner is looking for a general rapport with children and wiU be award-
Ing marks for it, since after all it is a paediatric examination.

General inspection Bend down or kneel to the level of the abdomen and with the flat palmar
1 aspect of your hand superficially palpate the four quadrants in tum. Then
Observe the child from the end of the bed. Look for whether thriving or n<• re~at this with deeper palpation (being sensitive to sign!; of guarding
dysmorphic features, race (e.g. Afro-Caribbean for ~ickle':', As~an for ~lA• which are most unlikely in the short cases). Children will sometimes tense
saemia) and presence of a nasogastric tube. Telangtectasla,_ sptde~ .naev1 (I• their abdominal muscles making palpation difficult. Try flexing both knees
region drained by superior vena cava, that ~s, ~hove_ the rupple_lme). M ilot ln order to loosen the abdominal muscles. Any masses should be delineat-
than three spider naevi are signifiqmt (chrome ll'\·er dtSease, atax1a telanglv ed and measured approximately.
tasia or hereditary telangiectasia). . .
In order to impress your examiners look also for comphcattons of l You must now palpate for organomegaly. First palpate the liver starting
diseases such as erythema nodosum, arthritis. iritis or complications o f trt~l from the right iliac fossa and work your way up. Try and synchronise the
ment such as the cushingoid features of steroid use (e.g. 180), gum h~fh 1 palpation with the chi!~ taking a brea~ in, and try and feel the liver edge
phy seen in ciclosporin use (e.g. post-renal transplant) (also seen in phenytnl flick across your fingertips. In younger children a liver edge that is soft can
use and M4, MS, AML). usually be felt up to 1-2 finger breadths below the right costal margin and
llnonnal ·
Then palpate for the spleen again from the right iliac fossa and again
Abdominal inspection l)'nchronising with deep iriSpiration. In 6rder to facilitate feeling for an
Inspect the abdomen fully including the flanks for scars (don't forget ' ' enlarged spleen tum the child over on to their right side and palpate again
_ angle and liver biopsy scars), distension (the Fs), caput medusae, umbllh .Wth the child taking a deep breath (your free hand should be on the left 163
162
to keep your hands still and look at the examiner and not the
side of the rib cage in order to stabilise it). It may be just palpable in an
infant; however a palpable spleen in an older child is neYer normal (since
'On abdominal examination .. . . First mention a gent!ral observation:
it must be three times its normal size in order to ~ felt on palpation).
HUII\p.le 'Charlie looked well/ thriving/ thin/ obese'.
Now palpate for the kidneys. This is always done bimanually with·the
mention the following whether they are present or not (since they are
left hand over the loin posteriorly and the right hand palpating deeply
to the differential diagnosis): Presence or absence oi jaundice,
anteriorly. Perform one side and then the other. In infants the kidnevs are
and dubbin!!;. Also mention any other findings such as scars, spider
often felt normally and this is sometimes facilitated by flexing the ruJ,s. • umbilical hemia if present.
->ca -Percuss the child's abdomen over the main quadrants and over the liver
and ~pleen. Remember to percuss out the upper border of the liver in sus-
you can mention the findings on the examination of the abdomen
~nding the results ot palpation, percussion and auscultation: this
·~ pected hepatomegaly since hyperinflated lungs may push the liver down you sow\d confident and coherent. A model example would be: 'Tht>
:I causing this apparent ht>patomegaly. (Some children might be scared so it was generally soft and non-tender apart from a smooth mass that
en is always worthwhile waming them before that 'I am going to make you be palpated 5 em below the right costal margin which moved with res·
~ sound like a drum'. ) could not be got above and was dull to percussion with no abnormal
E -Now you must auscultate the abdomen listening for bowel sounds and
llllllte~d sounds.'
ca formulate a diagnosis if you ca!': 'These findings are consistent
>< bruits especially over the aorta, renal arteries and liver and any masses that
w you may have palpated. You can use this time to start putting your find·
hfJ)atonle~:aly.' In the short cases this is probably as far as you can go
u done a complete examination. However you will probably be
'i: ings together in your mind.
as to the possible causes of hepatomegaly in the child.
:!
"C
- If the abdomen is distended or there are signs of chronic liver disease then
Cl)
ca
you should test for ascites. This is done intwo ways:
Q. 1. Shifting dullness: Starting from the umbilicus percuss towcuds the
flanks ~d mark the skin over which dullness was first heard. Then
hlm the child on to that side and again percuss as before and see if the
dullness has moved significantly towards the midline (implying the
presence of fluid in the peritoneal cavity).
2. Fluid thrill (positive only if there is a large amount of ascitic fluid):
P lace one hand on one side of the abdomen and then flick the skin o f bIa usually possible to be able to get a hand above a kidney but this is not
the contralateral side to see if there is transmission in the form of a po.ible with an enlarged spleen.
thrill. However, since it will also be transmitted by the subcutaneous
fat, politely ask the examiner's assistance (or child if old and
h $pleen usually enlarges along a direction that approximates to the line
. .de by the ninth rib (diagonally from the left costal margin to the right
cooperative enough) to place a hand vertically in the midline pressinu
gently on the skin.
lilac fossa). .
- I t is now essential as part of your paediatric abdominal examination thnl
the kidneys can be ballotted bimanually but this is not possible with a
apleen.
you sit the child forwards to inspect the back for scars and signs of sp w
bifida/occulta (which may be responsible for an enlarged bladder or fat • the case of an enlarged spleen it is usually possible to palpate the splenic
cal soiling, etc.). 411kh on its leading border (however the notch may be absent in the
J~~Unger child).
-You must then tum to the examiner and say that ideally you would al~~oe
like to examine the genitalia, the anal area and look for herniae and ptt ~ is usually dullness to perc'llssion .over an enlarged spleen but this is
fonn a rectal examination to complete the abdominal examination as wtll so in the case of an enlarged lkidney which is retroperitoneal and there-
as plotting the height and weight on a centile chart. The examiner will u-•• has resonant bowel over it.
ally say: 'No, that's fme.'
the following patterns •of clinical signs indicating disease
Presenting to the examiners ic liver dise<~Se
By this time you should hopefully have some sort of idea as to what you"''"' lee, pa lmar erythema, clubbing, leuconychia, spider naevi, foetor
lkus from breath, hepatomegaly, splenomegaly (secondary to possible 165
.; 64 the pathology is. Now comes the all·important presenting to the examlnt r
portal hypertension), ascites. caput medusae ( d
sion) and peripheral oedema. secon ary to portal pyper es of enlarged kidneys
In addition if you have picked up on th . · _.
for a cause f r ese signs, go a step turther and I
I . • ? exa~p~e Ka~ser-Fleischer rings in Wllson disease, or din' dron~phrosis. kidney with cyst or cysts, tumour le.g. Wilm tumour), renal
ung diSease m cystic fibros 1s. In thrombosis.

Chronic renal failure


literal enlargement
-
.~
Pallor, sometimes uraemic colour to skin (le
· I d' ' nc
.
peripheral oedema, pleural effusions pe . ardi~on tinge). !'ulmonary
tis, scars relating to renal$
ronephrosis (e.g. posterior urethral valves), stones, ureterocoeles, poly-
kidneys, tumour such as Wilm tumour (remember that 5-10% are bilat-
gery, pentonea talysis scars, AV vascular access sites NB An 'd
~ renal disease sho ld · tin- . 1
u ms ctive y lead you to take the blood
• v ev1 enc~ 1), also infiltration sec.ondary to leukaemia and lymphoma.
-
:::s the urine if provided). pressure (and
t/)
lhtr masses in the abdomen
..
ct
hne may include: faecal impaction (~etimes indentable). transplanted
E
cv
Causes of hepatomegaly and splenomegaly klney (with overlying scar in the lower abdomen). palpable bladder
>< ~ p~ominantly hepatomegaly or splenomegaly, indicated asH or •mine back for spina bifida), right iliac f0$sa mass in Crohn disease and
w tively m bracke~ after the conditien H nos or H &L.-- he
5 4·' =-!"!~

-(,)
·a:
.~
"0
Cl)
cv
seen.

Haemolytic
· ulCla patosp1enomegal

Sickle cell disease (~) felt be~re splenic infarction (which occurs at 2-4
/\RDOMINAL SCARS -:·:. · - . .. ~- .. ~·-·

YtiU should have a basic knowledge of the common scar.S that you may
., · ... · ..

n.. of age), thalassaenua,·herecbtaJy spherocytosis (S). Y unter in the examination.


A common scar is the so-called gridiron scar over the RIF which runs par-
Infections allel _to and above the inguinal ligament and is the result of a previous
- BacteriD/: ba~~erial septicaemia, brucellosis, tubeoculosis SBE (S) 1pPeuriicec iom y. ·
- Viral: hepahtis AI, B, EBV, CMV . '
-Proto~/: toxoplasmosis, maiaria_ (S) A' laparotomy scar usually takes the form of a midline, right or left para-
median scar and implies exploratory or major abdominal surgery (e.g.
- Paras1t1c: hydatid disease, schistosomiasis.
bowel resection in Crohn disease).
)\-fetabolic A so-called Kocher incision in the region of the liver implies hepatic sur-
-Storage disorders: mucopolysaccha ·d li _ aery, for example Kasai procedure for biliary atresia ~see notes earlier in
disorders (H) Q oses, P•doses, glycogen storage chapter). Smaller scars may be found in the region of the liver and may be
-Others: ~ilson d~sease, galactosaemia (H), alpha-1 antitry sin defici the result of liver biopsies for the investigation of liver disease.
(H), cystic fibros1s. Reye syndrome (H). P enr A scar in the lower abdomen may be the result of a transplant and you
Congestive cardiac failure lhould be able to feel a kidney beneath it. Renal biopsy scars are small and
luca ted on the back o\·er th~ loins.
Neoplastic causes
Hepatic tumours primary and secondary (H) le ka . l Small scars on the lateral aspects of the sides of the abdomen (usually on a
roblastoma. • u em•as. ymphoma, 1 line between umbilicus and anterior superior iliac spine) may be the result
of pre,·iuus pt!ritoneal dialysis. In cases of suspected chronic renal disease
Gastrointestinal look for arteriovenous fistulae (usually on the anns.and they should have
Chronic hepatitis (H), biliary atresia (H) inflarnma . an associated thrill and bruit if functional).
hypertension (usuallv S but depends • )tory bowel dJsease, PC' Colostomies are usually flush with skin surface and are usually in the
posthepatic. . on cause prehepatic, hepatic
region of the left iliac fossa. Ileostomies usually protrude slightly from the
tkln's surface and are located in the right iliac fossa (performed usuaUy in
Chronic diseases the treatment of mo and proximal colonic obstruction). Both types can be
166 SLE, }CA. temporary or permanent. Examine the surrounding skin for excoriation
1nd the scar itself for dehiscence or herniation. 167
ndocrinology
7
tHYROID DISORDERS .

"'rroid physiology
rl\e thyroid gland begins embryologically as an outpouching from the
lllor of the pharynx and migrates caudally to its final position in the lower
ntck anterior to the trachea. This is the pathway o(the thyroglossal duct
tleJn the foramen caecum of the tongue (junction of anterior two-thirds
and posterior one-third of the tongue) down in front of the hyoid bone to
IM thyroid gland . Remnants of the thyroglossal duct may present in the
lorm of.a cyst, sinus or fistula (mostly in the midline and move with swal-
lowing) . Iodide ingested in the food is actively concentrat'ed in the thyroid
1land. Peroxidase converts it into iodine which is then incorporated into
tyrosine residues in thyroglobulin using peroxidase. The tyrosine residues
ere either iodinated at either one or both ends (producing monoiodothy-
ronine - MIT - or diiodothyronine - DIT). Coupling then occurs and MIT
may combine with orr to form triiodothyronine (T3) or two DITs can com-
ltlne to fonn "'tettaiodothyronine (T4). The thyroglobulin is then secreted
Into the colloid for storage and under the influence of TSH endocytosis of
thyroglobulin together with hydrolysis liberates free T3 and T4. All T4 is
produced from the thyroid gland but 85% of T3 (considered the active hor-
1\one) is derived from peripheral conversion of T4 (by the enzyme 5'
lftonodeiodinase). The hormones are bound to thyroxine binding globulin
(1'BG) and albumin and it is the free component which is biologically
ACtive.
A negative feedback loop exists between TRH (hypothalamus), TSH (ante-
rior pituitary) and thyroid hormones. The thyroid hormones control the basal
lftetabolic rate, affect growth, mental development; sexual maturation and
~rease the sensitivity of beta-receptors to catecholamines.

- Chan.~es occurring at birth: At birth there is an outpouring of TSH from the


pituitary gland resulting in very high levels of TSH which usually fall to
adult levels by the end of the first week (and this is followed by parallel
changes in T3 and T4levels).
Congenital hypothyroidism
nervousness and irritability, fatigue, increased sweating, diarrhoea,
This is. a comm~'"! slide question and you should be able to recognise it (it may ated appetite, dislike of hot weather, palpitations, tachycardia, fine
:-ometimes be difficult to distinguish from a Down baby on a picture slide). It 1ur, hyp~rrdlt?,..,ia, proximal myopath)-·, goitrl:!, thyroid bruit and lid lag
1S most ~ommo~ly :a used by agenesis or dysgenesis although there may also 11td by sympath~tic overactivity). It is most commonly a result of
be. ectopic ~yroid. tiSsue present ~the majority of cases are sporadic). In agen· Vtl disease and this is caused by thyroid stimulating immunoglobulins
m
~lS there will obv1ously be no go1tre. In the minority of cases (about 5%) there Ia) directed against the TSH receptor. Females are more commonly ::::s
1S a dyshormonogenesi~, ~d a goi~e will be present, the commonest beillg ltd (F:M 5:1). Additional features of Graves disease include pretibial a.
-~ P~nd~ syndro~e. which IS assoc1ated with sensorineur;U deafness (often tOidema and Gra,·es ophthalmology (chemosis, diplopia and !!Xoph-
0
0
::!.
euthyroid). Other <:auses include pituitary failure and maternal illgestion of llllos). Other causes of thyrotoxicosis include a toxic adenoma, subacu:te
~
::::J
goitrogens during pregnancy. rolditis (often painful goitre) and initially in Hashimoto thyroiditis. 2.
::::s bnent may require carbimazole (or second line propylthiouracil); 0
Cl) . Clinical features include coarse facial features, dry s kin, prolonged jaun·
dice,. large fontanel!es, posterior fontanelle (> 1 ern), cutis marmora ta, brady· ranolol is used especially for thyroid storm. Thyroidectomy and radio-
cc
..
c(
cardia, h~potherm1~, h~rse cry~ .cold extremities, hypotonia, lethargy and lyt Iodine in older patients.
'<
E p~r ~eedmg, constipa tion, umbilical hernia, macroglossia and oedema. The
cu
)( bram 1S extremely sensitive to the presence of thyroid hormones from the end atal hyperthyroidism
w ~f pregna~cy until the first few weeks of life and if left untreated may result ahould bt> aware of the rare case of neonatal hyperthyroidism caused by

-0
·.::
-~
"C
Q)
cu
m trreverstble mental retardation.
Screening involves testing for serum lSH levels at 7 days of life (following
the postnatallSH surge). The lSH levels will be very high(> 20 f..lmol/1, most
> 50 J.LmOl/1) but be aware that ~ method will not pick up hypothyroidism
transplacental transfer of TSis. It occurs in 1-2% of cases of maternal
tVtS disease. Remember that since the conditiQn is caused by immunoglob-
and not th}'TOid hormone transfer the mother may not be clinically thy-
around the time of birth. The baby presents within the first week with
a. c~~~ by a low lSH (pitu.itary failur~). You should also be alerted to the pos• lability, diarrhoea, temperature instability, tachycardia (sometimes
Sibtlity of a n:ore generalised hypopttuitary problem if in addition there a ventricular tachycardia), diarrhoea and weight loss; there may be fea-
hypoglycaenua, small phallus or midline defects (see later in this chapter). of heart failure. The d~se is transient and disappears with the disap-
rance of the antibodies, usually within 2-3 weeks. .
Juvenile· hypothyroidism
nr,roid storm may occur if thyrotoxicosis is undetected and left untreated
A qu~sti~n may describe a child wh~ may be short for his age, suffers from lnd it:presents with fever, tachycardia, irritability, sweating and dianhoea.
c<:'nstipation, has recen~ly beco.me l~ss sociable, and recently gamed w eight, blat with i.v. carbimazole, i.v. beta-blockers and rehydration.
his school performance ts detenorating and he is intolerant of cold. There may
~lso b~ a presenting. g~itre. These features should point you ill the direction or
JU~.enile hyp.oth~roidtSm. These children have typical facies with pale dry •
s~ and penorbital puffmess. They may be short. Typically there is no eff«l ID!tre may be classified as: (a) toxic goitre- Graves disease, toxic adenoma,
on m.tellect (compared with congenital hypothyroidism). Causes include 1ilcute thyroiditis, toxic multinodular goitre; (b) non-toxic goitre -
~as~oto thyroiditis (more common in girls who may have initia l thyrotox lmoto thyroiditis, simple goitre of iodine deficiency (especially at puberty
1cos1S. or be ~uthyroid or hypothyroid at presentation). Hashimoto may Ill. 111N there are increased requirements), ingestion of go itro gens, inborn
associated Wtth Down, Turner and Klinefelter syndromes as w ell as SLE and of metabolism caused by dyshormonogenesis, or euthyroid goitre, a
o~~r au.to~une diso~ers. Hashimoto is the commonest cause of hypothy le colloid goitre, common ill the second decade, that may resolve spon-
~tdtSm m child~en. A go1tre may be present initially with no clinical features or sly in later life or become a multinodular goitre.
dlS~d thyro1d function at first. Antithyroglobulin and antimicrosomal anll
bodies are found. Bone age is delayed. Other causes oc 1·uvenile hypoth ·d"
. d d . ti f . · · yrOl ISO\ gations of thyroid function
m u e mges on o _gQttrogens, mdme deficiency, hypothalamic/pituitary dl•
order (secondary hypothyroidism - TSH low) and post -tllVroidectomy fiH: Nornal range 0.4-4.0 J.Lmol/1. Raised in primary hypothyroidism
Treabnent is with thyroxine. • lnd low in secondary hypothyroidism. Low ill thyroid hyperthyroidism
I'd raised in pituitary hyperthyroidism.
Hyperthyroidism
.,., T3 and T4: This gives measurements of thyroid hprmones bound to
!his is describe~ ~s primary with decreased TSH and secondary w ith ltlftding proteins and thus are unreliable since they can be increased by, for
170 mcreased TSH (pttmtary). It may present with weight loss, increased gro\Ytlt .-ample, oestrogen treatment and decreased by protein-losing states such
nephrotic syndrome. 171
enzy~e (ACE) in high concentrati~ in the lungs, causes the con-
of angiotensin I to angiotensin II. Angiotensin ll improves the renal
Table 7.1 Examples of typical results obtained by: (a) increasing the production of aldosterone; (b) directly causing
in ~ TRH stimulation test ~lllllnl'tricti~e~n; and (c) stimulating thirst. Aldosterone acts on the distal con-
Minutes after TRH injection 0 20 60 tubule to cause sodium and water reabsorption (in exchange for potas- m
TSH (hypothyroid) 4.7 24 59 or h ydrogen ions). :::J
c.
Cl) TSH (hyperthyroid) 0.8 1.2 0.7 zona fasciculata and reticularis produce glucocorticoids and andro- 0
"C TSH (hypothalarylic) 13 4.1 6.7 (")
•pectively. The release of these hormones (especially cortisol) i$ under :::::!.
:::J
(!) n- at hrP feedback controlled by ACIH released from the anterior pituitary :::J
(which itself is controlled by CRH release from the hypothalamus). 2.
~ -Serum free T3: Rises early in thyrotoxicosis (d. T4) and so is more ;,.,.,..n•t•~o~~a.·• has a diurnal variation with highest levels at 9 a.m. and lowest levels 0
(Q
·~ in detecting thyrotoxicosis. '<
:::J
U) -Serum T4 falls earlier than T3 in hypothyroidism and is thus more
<( tant in detecting hypothyroidism. adrenal hyperplasia
E - TRH test: This may be a data interpretation question and you will question relates to congenital adrenal hyperplasia (see Fig. 7.1).
expected to recognise the main graphical types. This test is used if commonest enzyme abnormality is the 21 hydroxylase deficiency
"'><
w patient is suspected of having thyroid disease but the TFTs are uvc••llar11ting for 95% of cases) in which progesterone and 17 OH progesterone

-
u
't:
.!
"C
Cl)
It involves the measurement of TSH levels before, 20 min and.60 min
TRH administration. In normal individuals the TSH l~vels rise l>y 20
(by 1-20 J.liilol/1) and fall to normal levels by 60 min. In primary
roidism there is an exaggerated response, with very high levels of
be. converted to deoxycorticosterone and deoxycortisol respectively,
in failure of production of aldosterone and cortisol with excessive
production. The reduced cortisol production results in increased
secretion which causes adrenal hyperplasia and excess precursor pro-
~
continuing to rise even after 60 min. In hyperthyroidism there is a as well as testosterone hyperproduction. The second commonest
response (because of inhibition by thyroxine) and in hypothalamic aeficiency is that of 11~ hydroxylase deficiency which prevents
there is a delayed response {see Table 7.1). and deoxycortisol being converted to aldosterone and
respectively. The clinical presentation of this condition is usually in
-Autoantibody screen: Graves - thyroid stimulating immunoglobulin ••.....,,,.+:•l
thyroid growth immunoglobulin (affects size of goitre}, thyroid period. Common presentations include:
mological immunoglobulin (causes eye signs); Hashimoto llnital hypertrophy in the male and in the female with hypertrophy of the
antimicrosomal and antithyroglobulin antibodies. tiiDris and labia, and labial fusion (which m ay present in more severe
_ Bone age: Delayed in hypothyroidism.

- -Ultrasound: If nodules are felt consider ultrasound.


*
-..s with ambiguous genitalia). The genitalia may display pigmentation
several weeks because of increased ACTH secretion.
---lo5ing crisis presentation in about 70"k of the 21 hydroxylase deficien-
- Thyroid scan: Detects uptake of pertechnetate (hot areas). Useful to variety (whi~ may occur from about day 3-4 up to about 3 weeks).
ectopic thyroid tissue.
1• •11101 -Pregnenolone - 1 1 OH pregnenolone - Oehydroepiandrostenedione

Adrenal physiology 1 1
Progesterone - 1 7 0H progesae!OIIe
1
Androstenedione
The adrenal gland has two main regions: (1) the adrenal cortex; (2) the
nal medulla. The adrenal cortex in fetal life produces cortisol and
droepiandrosterone (DHEA). After birth the cortex has differentiated inlt 11 ~
..1 1
11 Oeoxycoltisol
.l
Tntosterone
zona glomerulosa (outermost), zona fasciculata (middle) and
(innermost). Their function is in the production of: (a) glucocorticoid
mineralocorticoids; (c) androgens.
The zona glomerulosa produces mineralocorticoids (aldosterone). ItA
l
Aldoslen)ne
1
Cotlillal
t A simpJified bioc:hemical pathway demonstrating the main causes of
duction and release is under the control of renin (released from the
~renal hypefplasi;t.
response to reduced renal perfusion). Renin results in the rnonv•:>r<:t'"
172 angiotensinogen to angiotensin I which, as a result of the action of angiolt
It presents with hypotension, features of dehydration, vomiting, shock (or failure to increase dosage with periods of stress such as
collapse. An· early sign is an increase in serum potassium even before or surgery), Waterhouse-Friedrichsen syndrome (bilatera~ adrenal
ical signs become evident. Remember that the biochemical pattern of a lollllth<tge secondary to septicaemia most commonly resulting from
sodium and high potassium may occur with acute renal failure as well•llcM:occatenrU.a,).
aldosterone deficiency and diabetic ketoacidosis (however in the latter m
::J
dosis is present and the potassium is often normal - despite total bodl•k forms c.
potassium being depleted). disease, tuberculosis (may be noticed as adrenal calcificatio~ ~n X- 0
Jemember piwitary /hypothalamic causes of adrenal insuf~tctency n
::l.
'ii c. Hypog.lycaemia. to as secondary) as a result of lack of ACTH (through surgery, trau- ::J
> The 1113 hydroxylase deficiency presents less commonly with salt-losing or tumour).
0
·~ and hypotension (in fact hypertension is more common) since the build--uo •
0
(Q
::J '<
en 11 deoxycorticosterone appears to protect against hY'l'Otension as well as features
c( ing hypokalaem.ia (since it has some mineralocorticoid activity). Partial onset look for a precipitating cause with compounding hypoten-
exist where there may be no symptoms until puberty when females may Pl1'41L111llt loss and collapse. Abdominal pain (epi&~tric), vomitin~, hypogly-
E ent with ame~orrhoed and hirsutism and males with precocious with metabolic acidosis, hyponatraemia and raised potasslum.
ns
)( Delayed clinical presentation also includes excessive growth, but because chronic form there is a slow orset of generalised fatigue and weak-
w

-
premature epiphyseal closure the final height is lower than expected. anorexia, nausea, vomiting, abdominal pain, diarrhoea, postural
CJ
·c: and pigmentation of pal1nar creases and buccal mucosa (if
-Investigations (here we will discuss the two commoner varieties): Raised ff · )
.! OH progesterone levels in 2lOH deficiency and raised 11 deoxycortisol is high, this is not found in secondary causes of adren~l insu_ loency .
"C IStii2altiOI\S include biochemistry: lhere will be low sodlum, high potas-
Q) 1113 hydroxylase deficiency. Urine chromatography may also be used
ns look for . raised urinary 17 ketosteroids (androgen metabolites) low blood glucose. .
0. decreased 17 hydroxycorticosteroids (cortisol metabolites). may be a normocytic normO<hromic anaemia: primary dl.Sease -
secondary disease -low ACTH. The short synacthen (an ACTH
abnormalities will depend on the enzyme defect and in 21 OH 1
if of the salt-losing type: low sodium, low glucose, high potassium, test will help in diagnosin~ adrenal insufficiency btlt the ong
bolic"acidosis and high urea and haematocrit. In 1113 hydroxylase test differentiates primary (airenal) and secondary (hypothalam-
cy there may be hypokalaemia. In addition you may want to perform causes. In the short synaclhen test a dose of synacthen is given
1 and in adrenal insuffi<iency there is no increase in cortisol
tests to exclude other causes of ambiguous genitalia (see later)_. 10
• 1bC Lucs..uy • . • •
JO min. In the long synacthen teit a depot intramuscular U\)ection JS
- Treatmeut acutely involves resuscitation with i.v. fluids such as daily for 3 days and cortisol mea;urements are made subsequently- In
saline, :glucose and intravenous hydrocortisone. In the long term disease there will be no incre~ in cortisol but in secondary dJSor-
should use regular treatment with hydrocortisone and a salt-retaining will be a slow rise (as the e-.sentially functional but hypotrophic
eralocorticoid such as fludrocortisone in order to prevent contin are 'kick started' into action). Renember that Addison disease is asso-
ACfH-induced hyperplasia whilst also allowing adequate with other autoimmune diseasES, thus an autoantibody screen may
Monitor treatment with serum or salivary 17 OH progesterone useful.
Further treatment involves assessment of the genitalia and the is cau1ed by renal unresponsiveness to
need in girls for surgical correction. resulting in very high le'lels of renin, aldosterone and conse-
You should be aware that the salt-losing crisis may sometimes be mistaken hypertension (because of angotensin ll) with hyponatraemia_ and
a urinary tract infection or hypertrop~~ pyloric stenosis (howeYer the levels of potassium. It may :>e mistaken for CAH but there 1S no
chemistry may help you differentiate the contlitions).

Adrenal insufficiency
This is not common in childhood but be aware of its ~ode of presentatl1•••
which may be acute or chronic. ..laU54:!5 of Cushing syndrome are: (a) an AcrH-secreting tumour of the
i•illlb':V (Cushing disease); (b) adrend adenoma/carcinoma secreting com-
Acute forms 0ow ACTH); (c) ectopic ACTH ,reduction from, for example, Wilm
Congenital adrenal hyperplasia/hypoplasia, following severe hvpoten~~~ ~lr.lll,., •. (d) rarely hyperplasia; (e) ex<>£enous steroids (the commonest cause).
174 trauma or sepsis, or chronic steroid administration followed by fasciculata ~ mainly involvet 175
Clinical features
Thinning of the skin with purple striae, easy bruising. pigmentation if
~xcess, centripetal_obesity (moon face, buffalo hump, protuberant abi:io1m•.r.::'"SJX<:ae~l:~
h.mb mus~le wastm~ (leading to proximal myopathy), hypertension finding of hyperglycae.mia on blood testing (often following a prompt
ary to sochum ret~ntion (cortisol has some mineralocorticoid activity and finding glycosuria on dipstick). Glycosuria with a normal blood glucose
also hypokalaemaa and metabolic alkalosis), osteoporosis and peptic a problem with proximal tubular reabsorption (but is also seen in m
j
And_rogens may lead to hirsutism and a01e (especially in adrenal individuals, about 1% of the population, who have a reduced renal Q.
caronoma) and psychiatric disturbance. for glucose and is called renal glycosuria). 0
0
c; Mv"r"W>•ral·o.rr;,pnr~i;, has inanyc'!uses including: (a) pancreatic disease.:. cystic ::::!•
.2:: :;:,
Investigations haemochromatosis, pancreatectomy, chronic pancreatitis; (b) 0
~ (a) Usually c':'rti~l is highest at 9 a.m. and lowest at midnight. InC disease- Cushing syndrome, growth hormone secreting tumour, 0
:;:,
en s~ndrome thlS daurnal rhythm is lost; (b) 24 h urinary cortisol levels roboxic~>is, pha~ocytoma; (c) drugs - steroids, thiazide--diuretics; cc
'<
< h~gh; (c) d_examethasone is a synthetic glucocorticoid which in normal '""·..ri·h><i disorders sti'i:h as Friedreich ataxia. Other causes include infec-
vJduals ~mds to cortisol receptors in the pituitary gland and (especially associated with high fever), stress, intracranial tumours/
E decrease m ACTH secretion reducing cortisol production (sometimes and following seizures. Hyperglycaemia is accompanied by
cv
>< ured as urinary 17 OH corticosteroids) by the adrenal glands. The (secondary to an osmotic diuresis).
w (low . dose) dexamethasone suppression test will distinguish clinical history of a few weeks of increased thirst, polyuria, weight loss

-
(,)
'i: Cus~g syndrome and stress, obesity and depression. In the last lethargy in addition to excluding features of the above causes of hyper-
(whlch can sometimes mimic Cushing) the serum cortisol will become will help you make your diagnosis of DM. Remember that infec-
.!2
'0 ered by the dexa~ethasone (but not in Cushing). In the high dose may accompany the presentation of diabetes (leading to pruritus vulvae
(J)
cv ~thasone suppress1~n test cortisol is supp'r essed in Cushing disease butMIIPailanitis You may be given data relating to a high plasma osmolality with
Q. m adrenal o_r ectop~c causes of Cushing syndrome; (d) biochemically sodium, potassium and urea and thus the remaining osmotically
may. be a hi~ sod~um and low potassium and plasma glucose may particle contributing to the hyperosmolality must be glucose (see
be high; (e) m the msulin stress test (see later) the cortisol should 10).
more than double the normal baseline in normal individuals - this
rise does not however occur in Cus~g. Treatment depends on the Smogyi effect
and tumours may require surgery (such a s adrenalectomy or is a fairly common question which relates to the child who appears to be
noidal microadenectomy). BreU-conb~ol!led diabetic (the question may give you clues to this such as a
glycosylated haemoglobin. no glycosuria in clinic visits, a reliable
and well informed and sensible parents). There is, however, early mom-
glycosuria and ketonuria. On closer investigation there appears to be an
Diabetes questions come up regularly but there appears to be a familiar ate dosage of insulin for the age/weight. This may have prompted an
toire of topics relating to it. ~tea~;e in insulin dose administration without improvement in glycosuria or
...,.,,.......... The likely cause is the Somogyi ·effect ·wruch describes the. ·phe-
Basic physiology • neriOn where the child experiences night-time hypoglycaemia (although
may also occur during the day as well). This may .manifest as nightmares,
Insulin is an anabolic hormone whose main action is on muscle and and rarely fits though usually no manifestations are present but it sets
tissue where it causes uptake of glucose and promotes its storage as motion compensatory hormonal mechanisms which lead bo rebound
It also causes up~ke of amino acids, stimulates protein production anti rrM>TVtvr~•P"rl'"' with the resulting glycosuria and ketonuria. It can be inves-
m~tes fat synthesiS: Whe~ insulin is lacking these processes go inro by a 2Zf ti urine colle~_tion (ideally every 4 h) whiCh ·shows exc~ glu-
~·th hyperglycaerrua causmg an osmotic diuresis and consequently in the urine ~uring the higtit time comp~l:ed with·day p,me, or preferaoly
tion, breakdown of muscle to amino acids (muscle wasting), breakdown ,.n•lvl,t blood glucose sampling.
~o g~ycerol and fatty acids and ketogenesis (lipolysis with P-<>xidation Somogyi effect is more common when fast-acting insulins are used.
m~ m ~etone_ ~rod~ction via acetyl coenzyme A) with consequent ..llmt!nt involves carefully reducing the dose of insulin or using a longer
acidosiS. Anti-msulin hormones include glucagon, adrenaline, cortisul insulin. Other causes of finding early .morning glycosuria are: (1) non-
growth hormone.
_.,""''"cu•u:: with insulin regimen; (2) dawn phenomenon (hyperglycaemia
176 .177
m
:::s
Q.
0
0
:::!.
::l
-~ 0
0
cc
·~ '<
:::s
II)
<(

E
tV
><
w

-
(.)
'i:
.~
"C
C1)
tV
a.

178
usen by proxy (maternal exogenous administration).
pathways, o r disturbances in the insulin/anti-insulin hormone system. acid oxidation defects, camitine deficiency.
symptoms of hypoglycaemia are divided into two types:
Brst year of life transient forms are rommoner and are usually ketotic
a. Neuroglycopenic symptoms: Headache, irritability, confusion, seizures, coma. but sustained forms tend to be non-ketotic in 'natur~. From 1 year of
Jitteriness, apnoea and hypotonia in the neonatal period. forms occur more commonly.
m
::::J
•• cc:>mmo1nest cause of hypoglycaemia between the ages of 1 and 7 years a.
b. Adrenergic features: Tremor, tachycardia, sweating, hunger, pallor, ---......_ hypoglycaemia (accelerated starvation). It usually begins after the 0
n
changes. . :::!.
The causes of hypoglycaernia are also divided into two types: (1) and clinically presents after a period of prolonged fasting (typically
->ns ( ) non-ketotic.
2
··-··-··.., ..._ 7-8 h) and/or in combination with a concurrent illness (typically
frt:F ratio 2.:1.
::::J
0
0
co
·~ KetOtic causes hypoglycaemia (post-prandial hypoglycaernia) occurs soon after '<
::::J meal with blood glucose levels less than 3 mmol/L It is seen in up to
U)
H~re there is reduced glucose production and a corresponding low individuals and improves spontaneously.
<(
level. It is ketotic because insulin is lacking and thus lipolysis results in lci>ttoll411iR in the examination must be sought in order to de~ermine a possible
E body formation. Look for the features of Beckwith-WJedemann syndmme (e.g. macro-
ns -Low substrate levels: Malnutrition (including poor feeding after birth), macroglossia). Look for hepatomegaly found in glycogen storage dis-
><
w asphyxia, prematurity, IUGR, malabsorption, infection. These causes for evidence of hypqpituitarism (most commonly secondary to a

-0
'i:
."C~
Cl)
ns
the commonest immediacely after birth and are usually transient
resolve after appropriate treatment.
- Liver disense such as Reye syndrome.
or idiopathic) associated with short stature (height usual-
the third centile), delayed sexual characteristics, immatUre round
with midline defects such as cleft palate or optic hypoplasia.
should be taken for hormonal as5ay (insulin, cortisol growth hor-
a. - Enzymatic defects in gluconeogenesis and glycogenolysis: Von Gierke disease fatty acid metabolism indicators (ketones, free fatty acids),
type 1), galactosaemia (both disorders are associab!d with hepatomegaly). pathways (lactate, pyruvate and alanine). Urine during hypo-
should be tes~ for ketones. Urine should also be sent' for a drug
-Reduced levels of circulating anti-insulin: adrenaline, growth hormone, cotllllllcc:>lo•gy screen in selected cases.
sol, glucagon and hypopituitarism. of insulin levels during a period of hypoglycaem.ia is impor-
-Ingestion of drugs such as alcohol and salicylates (alcohol inhibits diagnosis of an insulinoma. firstly the presence of a low fasting
neogenesis but plasma glucose qm usually be maintained from together with a normal or high insulin level is.suspicious (that
breakdown). ratio is high). Then perform the insulin suppression test
~~unn is infused into a patient. Normally because of the hypogly-
Non-ketotic causes the insulin level falls, but this is not the case in an insulino-
•••,~vE~r insulin levels cannot be measured since we will not be able to
Here there is an excess of insulin (inappropriate because of low blood between the endogenous and exogenous sources. Thus C-peptide
cose): non-ketotic since insulin promotes fat synthesis and no ketone which is secreted from the B cells of the pancreas in equimolar
will be formed. to insulin. A plasma C-peptide concentration in excess of 1.2 ).lg/1 is
- Too much insulin administration in diabetics: including missed meals of an insulinoma. Measurement of C-peptide will also distinguish
t&a:~tOslS from Milnchausen by proxy.
excessive exercisE?.
- Infant born to a diabetic mother.
- Nesidioblastosis (thought to be caused by B-<:eD hyperplasia in the abnormalities are common accompaniments to many paediatric
creas and curative treatment may involve removal of part or ~hole of You should be able to discuss the causes, recognise the commoner
pancreas). .,...,""r-inc. and be able to investigate appropriately.

- Islet cell adenoma.


- Rhesus isoimmunisation.
- Beckwith-Wiedemann syndrome. 181
1~ -Islet cell insulinoma .
-Infnllcy: nutrition disease
- Chihilzood: growth hormone chronic diseases will result in poor growth. These include renal failure,
- Pubt.>rty: growth hormone and sex steroids. tubular acidosis, congestive cardiac failure and chronic severe asthma.
age will be delayed and if the underlying disease is left untreated then
The a'·erage rate of growth during childhood is between 5 and 7 em
will be a pcogressive deviation from the chronological age.
(increasing to 7-12 em/year around puberty). Growth can be m
using standard growth charts or growth velocitv charts. Growth :::s
c.
-~ charts will usually detect a slowing down in growth before it will t-e
ated_gn a normal growth chart.
0
n
:::!•
·~ . The mid~parenta_l centile gives an expected range for the child's "• R11nx>m·vrc>lOI and growth honnone deficiency (these two produce a delay :::s
0
:::s given the parental heights. bone age). Growth hormone deficiency children are short (a de\·iation from 0
UJ -Fr.>~ n boy: The mid-parental height is determined by taking the normal growth rate occurs after the age of about 6 months) with a doll- (g
c( '<
height+ 13 em and marking it on the height axis and then taking the fa face and may present with hypoglyc~a early in life. Provocation tests
E he~ght ~d mar~ it on the height axis. The mid-point between req\lired to confirm GH deficiency such as after 20 min exercise, o r
ns he1ghts lS the nud· parental height and 10 em on either side of this rtnsulin, glucagon, clonidine and arginine tests. See insulin stress test below.
><
w equivalates to the Jrd and 97th percentiles. Cushing syndrome and precocious puberty both cause an advancement in

-
(J
·~

."C~
Q)
ns
-For a girl: Take the father's height - 13 em and mark it on the
a':d the.n take the mother's height and mark it on the height
bone age. They result in an initial increased growth velocity but a final
~uced height as a result of premature fusion of the epiphyses.
mld-pomt between these two measurements is the mid-parental ...IQ'Ilypopuuuai presentsasshortstature,round face,saddlenose,shortneck,
and the 3rd and 97th centiles lie 10 em on either s ide of this poinl tmaU larynx with a high pitched voice, Small hands and feet, delayed sexual
Q.
Skeletal maturation appears to be more closely related to physical N!evelopment, microphallus and fine scalp hair and loss of body hair (indud-
ment than to chronological age. lng axillary and pubic cf. anorexia), pallor (as a re.Sult of loss of melanocyte-
ltimulating hormone (MSH) activity of AC1H) and hypoglycaeinia. The ca us-
causes of growth abnormality • are idiopathic or seCondary to trauma, radiation, syndromes associated
with midline defects, tumours (such as a craniopharyngioma caused by an
Normal variants expanding remnant of Rathke's pouch), infections and bleeds.
-Familial slw_rt statur~ J:Iere the parents are short. There is no delay In Remember that tumours in the pituitary gland cause, in addition, other
age and children contmue to grow along their centiles. . endocrinological disorders (either hypo-or hypersecretion d epending on
the nature o f the tumour), diabetes insipidus (posterior pituitary involve-
- Cons titutional short stature: M > F. Children are born with a normal
ment) as well as visual field d efects (classically a bilateral hemianopia) and
and length and then during the first few years of life the rate of
hydrocephalus as a result of obstruction to the third ventricle.
begins to fall. ~ is howeve r temporary and height eventua lly
normal. The~ IS a delayed bone age but serial bone ages will Psychosocial deprivatiora is known to cause reduced secretion of growth
advancement m parallel with the child's age. Children usuallv reach
mal adult height eventually, although growth may occur ~ell
teens after ha\·in~ no obvious growth spurt a t the time of expected
ty. The ~ne age 1s us~ally 1-4 years behind the chronological
appropnate for the he1ght. Puberty is often delayed. Often a Dysm~rphic children with syndromes such as Turner (perform a chromo-
ily history of a similar tempo of growth in one of the parents is analysis in a girl if suspicious of Turner syndrome), Noonan, Aarsog,
Ask about the age at onset of menarche in the mother since there t• ....~,.,,..._,'1\J ·
Russell- Silver and Down syndrome. Some questions may
family history of constitutional delayed puberty. The diagnosb you some meas1:1rements of the trunk and limbs (normal ratio is 1:1).
made when other diseases have been excluded. *"'•en:tbE~r that achondroplasia gives rise to a normal sized trunk and
limbs and spondyloepiphyseal dysplasia gives rise to a short trunk
Nutritional disorders normal limbs (spinal irradiation may also cause a shortened trunk).
These may be a result of reduced intake or malabsorption. children born IUGR or prematurely.
182
i83
lft_sirls). The oestrogen is mainly responsible for ~reast enlargeme~t, th~ red
flginal mucosa turning to pink, increased prommence of the ~ab1a mm~ra
Table 7.2 A typical set:of:results-o!nalned-~ollowin9 an insulin tolerance test
Illgirls and increase in penis size in boys. Pituitary gonadotrophms are m~m­
Minutes after insulin injiction 0 15. 30 45 60 IJ responsible for increase in testicular size. Adrenal androgens are mamly
Glucose concentration - -. 5.1 1.9 4.5 10.2 9.7 Ntponsible for pubic hair and virilisation (facial hair, arne, deepening voice
GH - - ----2"}- y g 4.3 3.7 2.5 m
Cortisol ·~==,516~.,~ 931 886 611 498 1M increased muscle mass). ::::J
Q.
The order of pubertal changes in boys is as follows: testicular enlargement 0
may be determineti using a Prader orchidometer) with redd~nil:lg and n
........ ____
. . osity of scrotal skin -+ pubic hair.,.... penile enlargement -+ axillary hair.
:::!.
-~ ::::J
-.~-

£xamplt>: In this patient th~~ ·i ;,l;otit growth norriione deficiency and Cu5hing ; :order in girls is as follow~): breast enlargement -+ pubic hair -+ axillary 0
disease (see earlier explan'!tiO~~or,.~·~asons). '*tr-+ menarche. In boys and girls the growth spurt occurs during puberty. 0
CQ
·~ -;-Tanner staging is expected knowledge in the clinical examination. It '<
::::J Wttolves the assessment of genital development in boys, breast development
U) The insulin stress test _ _ _ ~·~~-
~Sirls and pubic hair growth in both sexes. All scales are fro~ I to V.
..
c:(
The insulin stress test is-a corru:nono-da~interpretation question. This test II
alSO used for assessmen~~Q.~Cpt~l$n_dwrolactin secretion in addition l~
E
ftS
)( growth hormone se<:retion. ·lt~issonly_c~rriec.. out in specialised centres. Insulin
w is injected and GH measureci.:.~t 1~,{30;~5, 60 and 120 min, with hypogly dtfined as the development of secondary sexup.l characteristics before 8 years

-0
·;::::
.!
"'0
Cl)
ftS
caemic symp~oms and si~~~~!fl5;30 min. There should be a reduc fl age in a girl and 9 years in a boy. It is much commoner in girls compared
tion in basal glucose .valiies3iy£m'Q.~~Io or < 2.2 mmol/1. If peak Gil l 'boys (F:M ratio 5:1). Eighty per cent of~ are not ~lated to pathological
levels are < 7 ml!/1 then -~'1~~.ts,;:_G_~~deficiency and levels in excess ol luses in girls, whereas 80% have pathologtcal causes m boys.
15 mU / l exclude the diagnesis.-In normal subjects cortisol leve ls should bt
d ouble the basat ·tevel (see· Table 7:2).~ Examples of other pituitary functioll ~ification ·.
D.
tests include the I..HRH and ,~;,tes~.:-=-___ True: J>uberty is synchronous: that is, it occurs ·in an ors;ierly fashion as
desCribed above (sugg~g an intact hypothalamic/pituitary axis)
The pituitary gland- 10metimes referred to as intracranial.
_ _-..=.:::::_.-:;;.-__ -

Secretion o f hormones .from the"'pi~iiary:-gland .. • Idiopathic.


• Secondary to trauma, tumours, haemorrhage, hydrocephalus,
-Anterior pituitary-gland: chr~~p~o~.c~lls- non-secretory; acidophil neurofibromatosis, primary hypothyroidism (the only cause of
cells - GH, prolactin;~~E.h:il:<;~lll>-... FSH, ACTH, Ui, TSH. precocious puberty with short stature and delayed bone age}.
- Posterior pituitary ~land:-Oxytoc_m, ADH.
False (pseudopuberty): Puberty is not synchronous and is pituitary inde-
.. pendent. Sometimes called extracranial.
Bone age (see also-Cb~Rte~·--1_1)-
• Adrenal: Cushing syndrome, congenital adrenal hyperplasia an d
- Cortisol: Cortisol exce5s -:::·<lelayea;·cortisOl deficiency - normal. tumours.
- Thyroxine: Thyroxine exces's - $lightly advanced; thyroxine deficiency .. GonJUiJ11: Ovarian cyst/tumour (~.g. granulosa cell}. Testicular tumour
d elayed. · - - · (e.g. Leydig cell tumour). Albright-McCune syndrome- cafe au lait
- Growth hormone: G row th hormone excess ~ no rmal; grow th hormone spots, polyostotic fibrous dysplasia (with irregular borders - 'Coast of
deficiency - <!_e~yed-=- _ M<Jine') and precociQI,lS.puberty ~used by pdrhary ovarian cy~ts.
-Androgens: Androgen excess - considerably adva nced; androgen secreting oestradiol (also assodat~ with Cushing ~d
deficiency- normal; hypothyroidism).
Ectopic: Gonadotrophin secreting tumour (e .g. hepatoblastom a,
dysgerminoma). Exogenous hormone administration (e.g. ingestion of
birth control pills).
Puberty is the consequence of th~ interaction of the hypothalamic/pi!
itary 1gonadal feedback loop. Hypothalamic Gn-RH results in pitull•t may ask you to distinguish the two forms. Remember that in true
release of LH and FSH (pituitary gonadotrophins) which in turn • ICOCiO\.IS puberty FSH and LH levels are high (you should also perform
gonadal hormonal release. P u berty coincides with an increase in the col'\1 and testosterone levels in an initia l evaluation and adrenal 185
1 ~ tration of circulating gonadal hormones (testosterone in boys and oestrntl
hormones such as cortisol and 17 OH progesterone might also be taken}.
pseudopuberty FSH and LH levels are low. . Often goes along with growth delay {see e~rlier)
A Gn-RH stimulation test with basal and peak LH, FSH and sex ct.....n.m 1r····
distinguishes true precocious puberty (resembling an adult response) fro O\IIIJIII<~t>JJnd(lfrl)p,lzic llypogtmadi:>m Decreased FSH and LH Deft"\:"tive hypo·
pseudopuberty (prepubertal response with low FSH and LH levels). In pituitary Isolated gonadotrophin deficiency which may b~:? idil~
Q)
or assOCiated with a -.vndrom nr t>'<amplt> Kallman wndromt>
m
"C with true precocious puberty the testes are almost always large but :::s
:::s pseudopuberty the testes are small{< 2 ml). Other useful tests may incl with anosnua, mtCJ'1'f'hallus....·vpturchldt:>m ~nd rt•nt~l dl:'ft>Ctsl. 0..
(!) 0
skull X-ray /MRI, pelvi.: ultrasound scan and bone age. Isolated prematu -:.\ ndrumt- Hv·pnthalam1.: · pltultdl"\ dam"~"' trauma .n!~< · n
~
::!.
thelarche (isolated premature breast enlargement) caused by ovarian 1rradtatl\ln tumuur-,. ,,m~emtal maltormatnm!>. ~Urj:l,~r~ Here utner :::s
is common and there are no other signs of puberty or advanced will usuaUv bE" affect~ in addition to g"madotruphin release 0
·~ 0
:::s !however these patients require careful follow-up). Pubertal chrt.,nk d~aSt' hypothyroidism, Cushing Jbt>ase. diabete~.
cc
f/) b common in boys passing ,through puberty, and usually coincides and in athlett!S '<
<( Tanner stages Ill and IV. It is caused by an increase in the oestrogen/ and
llypo~mtadtSII· ln'reased FSH LH l.>.:-ft.·t·tJq~ ~onad:>
gen ratio seen at this time and is sometimes tender. A full history
E examination usually excludes other causes. It usually resol\·es spont~ ..., .......~~
this mav be tht> [(>Suit \lf primary \Wanan t"ilun:> such a~ (l<·curs
cu svndroine Alsu ..~.>nsider chemotherapv and p,>-;t arradiat1on In
>< neously. Additional causes of gynaecomastia include: pituitary tumour, te
w ticular /hepatic oestrogen secreting tumour. hyper /hypothyroidism, tiv~,rP"!I""'-
this may be caused b) primary testicular failurt- such a:. cryp-
C) br Klinefelter syndrome. Also consider testicular feminisation .
·.::
.... disease, Klinefelter syndrome, testicular failure (if oestrogens > a~~4~:~~,!··-~~th~~~;y
."C~ feminising tumours and drugs (oestrogens. phenothiazines,
digoxin). Localised causes include: haemangioma, carcinoma, lipomas
- and post irradiation.
tions for delayed puberty_ include the following (most are
Q)
cu abscesses. to tests for ~hort stature) bone age. FSH. LH TFTs testosteron~ .
0.. You may be sho"'rn a slide of swollen breasts in a newborn baby. This Gn-RH :>timu)ahon test. HCGstimulation testiHCC b mjt!Ctt'd and
referred to as neonatal mastitis or neonatal breast engorgement rather release? tS measured from thE' testes). vtsual f1t?ld analysts
gyn:aecomastia. It is common and is a result of the effect of maternal oestto OOC!kmg at the pituttary fossa. dmo1d proc::e~ses ard tor cal-
gen on the breast tissue (occasionally 'witches'.. milk' may be seen from and cranial MRI (if hypogonadotrop~k hvpogonadtsm ts
nipples). Rarely it may be complicated by abscess formation when anltibiiotllr•lllllltled
become appropriate. ·
Premature adrenarche (isolated -pubic hair development) is also
and again follow-up is essentiaL Beware if in addition there is cliltor.nm,eiZilli
and other signs of masculinisation where you should consider the possibiiiiiiiNIIIPIC
of an androgen-secreting tumour.
Management of precocious puberty involves understanding the cau•l
and investigating appropriately children in which pathology is suspectl••l••iccati•on of arnbiguous ~nitalia
In the majority (especially in girls) little more than reassurance is requ
and investigation only in cases in which there are other suspicious feat\1 pseudohermaphrodite
or for example you suspect Klinefelter syndrome (perform a femaJP tXX) and normal intt>mal ducts but thert> is masculinisa-
Bone age will be ad,·anced in many of the forms of preco.cious puberty esl't E'"Lt>rn.ll g..-mtalia. Frt.)m Fig 7.2 wt> ~an~ that tlus may arise from
dally if there is adrenal involvement. The longer the exposure to andn-,gt.>n stimulation. '-iatemal cau~ include androgen expo-
steroids and the higher their concentration the more advanced will be first trimt>Stt>r. nr fTnm an andn~n ~-rehng tumnur Fetal causes
bone age. The most important long-term complication caused by cong..-n•tc1l "'dnm.1l h\perpla.-.&a
puberty (other than any underlying pathology) is accelerated growth
occurs initially, eventually leading to premature fusion of the epiphyses
a short adult height. · baby ss genetically a male (XY) with testes, but with ambiguous gen-
may be due to an inborn error of ·m etabolism of testosterone
defective 5-alpha ~uctase defioency CARl and the testicular
syndrome in which there is complete or incomplete deficiency of
This is defined as the absence of signs of puberty by 14 years in a boy and receptors (that is, end-Qrgan resistance}. In addition there can be
1.86 years in a girL testicular development with defects such as Leydig cell hypoplasia. 187
BIPOTENTIAL GONADS
(weeks 6-7)
lor a uterus. If present then this may be the result of abnormal testis such
.. Sertoli cell hypoplasia, or a true hermaphrodite. If not present then the

~
11uses are for a male pseudohermaphrodite listed above. If gonads are not

Q)
//
Females (In absence o1 TDFl Males (in presence ol TDf)
palpable the baby may be genetically male or female. In this case the ultra-'.:
IOWld looking for a uterus will differentiate between a male and female m
·-"C(!):::s l l
peeudohermaphrodite.
Apart from obvious parental distress caused by the ambiguous genitalia,
:::s
c.
0
Ovary Testis tlprime importance to the paediatrician is to exclude and treat lhe pot~tially 0
c; :::::!.
> l /""' lit-threatening complications of a possible congenital adrenal hyperplasia :::s
0
·~ Absence of MIH Leydig cell$ Sertoli celll -.cl salt-losing crisis.
MIH 0
Testosterone A common slide and grey case question in the examination is to recognise
en
<(
:::s
I
Wollfian ducts
\
Mullerian ducts Wollfian ducts
l •biguous genitalia. Subsequent questions ask for your list of investiga-
Mullerian eM llns. These are pelvic ultrasound, karyotype and measurement of 17 OH
cg
'<

~ids as the three main expected answers. In addition tests may include
E
ns
l
Involute
l
Fallopian tubes.
!
Vas ,jeterens.
l
lnvolutt ~G (to see if HCG stimulates testosterone release from Leydig cells on the
>< uterus. cervix. •tis) and androgen binding si~ on genital skin fibroblasts (for testicular
w epididymis.

-
upper 113 vagina seminal "119sicles. lllninisation).. ·
(.)
'i: eJacuJat:>fV duetS

.!:2
"C
1
Absence of DHT •
Presence :,f OHT Management
Cl)
ns
c.. l
Feminisation ot external
l
Mascutinisation of
VIva or grey cases may ask you to discuss the management.
First discuss the way that your investigations have narrowed down your
genitalia (weeks &-12) external genitalia .uterential diagnosis (slides often ask for three investigations of choice: ultra-
IDUnd 9f pelvis for uterus, karyotype and 17 OH progesterone). This may
TDF=Testes determining taCJC>r. MIH =Mullerian inhibitoty factor. OHT ,.. di)-drotestosl•tlfl lftvolve resuscitation of a shocked infant with a salt-losing crisis, continual
(testosterone is converted to OHT iri target tissue by 5-alpha reduc:tase) ~chological support to the parents and· advising against na.ming of child
tlltil all investigations and appropriate consultations have taken place. In
Fig. 7..2 A simplification of the events·that lead to sexual differentiation. .-mtion to having determined the genetic sex, decisions have to be made as
• what sex to rear the baby. These are joint decisions with surgeons, endocri-
.logists, paediatricians and the parents. It is surgically easier to ~onstruct
llnale genitalia compared to male genitalia, and so many genetic males are
There m ay be a structural defect such as seYere hypospadias unrelat~~l
red as females. If CAH is diagnosed hormone replacement is necessary.
androgen production.
tfychological support is necessary for parents in addition to support groups;
~etic counselling if th~ is a genetic cause.
True hermaphrodism
This is in practice extremely rare and occurs when both testicular and
an tiSsue is present and there is frequently ambiguous genitalia. They m•J •LIS•tS of micropenis
genotypically 46 XX (most commonly>. 46 XY or mO">aicism.
Idiopathic
Hypopituitarism with growth hormone <?r gonadotrophin deficiency
History and examination Hypothalamic disorders such as Kallman syndrome
The history should exclude maternal androgt!n ingestion or Testicular feminisation syndrome
neonatal death, for example CAH or familial genetic Other syndromes: Prader-Walli, NOonan, Down and Smith-Lemli-Opitz
Examination should in\'Ol\'e palpation of the gonads (a male J)Seulc.lllltML syndrome.
maphrodite may occasionally be contused with a female with bi
inguinal hcmiae). Blood pressure should be taken and vou should 1011~ of macropents
pigmentation (ACTH induced in CAH). (f the g o nads a~ palpated then
Congenital adrenal hyperplasia (look for scrotal pigmentation)
188 baby is definitely male. An ultr:~sound should then be performed to P~ocious puberty. 189
llllld overload. Sometimes an ADH antagonist such as demedocydine
• be used.
Syndrome o~ Hnappropttii:llte ADH S«i"eti~~ (S8ADH}
This is a common q uestion and should always be oonsidered in a child insipidus (DI)
presents with hyporiai:raemia (possibly wi~h dinic:al sequelae such a~ m
seizures) ;:md an ioappropriately concentrated urine. ADH is secreted fr..)TJl lu common condition in examinations and should be thought of in a child ::s
0..
th·:? pos~erior pitllttaty gl.anci in tCS~-'\:mse :.o hyperosrnolality or presents with polyuria, polydipsia, frequency, nocturia and nocturnal 0
(')
voYI·lemia. In 5~ 1 ~ DH t.ht•~-e is an hnppropriat~ SP.nel:ioH :..Jf ADH (il."l u,.:1r -"'· If drinking is continued and there are no additional fluid losses that ::::!.
ubs~nce of the ,_,~1..1al phy:;iological si'.itl'luli mentim~:!d aro" ~) that occurs in be kept up with, such as fever or diarrhoea, then dehydration will not ::s
However this balance is not always seen in prctctice (that is, dri.r-..king is 0
number o f cond itions. '-·· Clin f h 0
Causes includ""· (<') ;rthacr:u'lial <:<~uses sud\ :;.,; \~ad ir&jury, IIWays kept up) and dehydration will develop. · ica1 eatures o f de y- co
e>.lt."e[>halitis, sp<~ce--<Xcupying lesions, tumour. aPS""SS, lmematoma; (b) pul - including fever (especially in infants), constipation, vomiting and '<
n"''>nary causes - IPPV, pneurnoma, astn.''l\4 att<l-:k; (c) .zctopic hormon venous thrombosis - may occur with ironically good urine output.
oroduction _rare in ch.ildren, usually tumo uf!i in :t~d~• patients; (d) d rugs tests may reveal hypematraemia with increased u rea as well as a raised
earbanmzepirte, chlorpropamide, cyclophospn'L>flirle, v incristine, morphlnt and haematocrit. Usually a data question presents a patient with
rifampicin. Some children receive th~rapeutic DDAVP (e.g. in high urea and an unexpectedly low urinary osmolality.
enuresis) and this can cause an SIADH pictul.-e. Features include: insipidus refers to two conditions.
·-A }ow plasma osmolality with a low volume of inappropriately hypertonll tral Dl: Here there is a deficiency of ADH secretion from the posterior
urine. itary gland (idiopathic or secondary to hypothalamic disease, e.g.
opharyngioma), post head trauma, meningoencephalitis. Don't forget
-·A hyponatraemia caBsed by bci:h dilution cmd i1atrim-esis. tiocytosis X or familial causes- AD.
- A h.'gh uriJ\;1ry sodhl.m excretion > 20 mmt,: /!. This is secondary t<? relen DI: There is an insensitivity to ADH of the collecting ducts in
lllll:lhr£we:ni'c
of natriuretic peptides, firstly l:lecause of vniume receptor stimulation((! kidney. It m ay be acquired, for example hypokalaemia, hypercal-
antinat.rh.t.retic peptide (ANP) frmn the &tria), and secondly because sickle cell disease and lithium intake. It may occur following
fluid overload the.-e is J1.0 ren~n chive and C'Jns.2q_uer.tly no aldosterone pr polyuria for any reason (because of a reduction in medullary
ductio•., leading to urinary sodic.rri loss. tonicity) such as occurs in obstructive nephropathy, interstitial
--An !noease il"' t craJ body water '.ovithout the pre-<...enet? of oedema caused l and Fanconi syndrome.
s.o<.HU>1.\ loss. Na~er is d'$tribuled equaJly between the intraet?llular 111
extr<!CP.llular ,...~)Inpar! ~ne-nl·s
- Re..'iall~mct.io i.'lduaing GFR is •Jrwffecte<.A.
- L'i order t:.> .-,... .~-e the diagnosi~ ~t ls im XTtant to exclude hypc•vcola«~'ll'·!l.,aabE~tes
1

(din;cally as pedusion, pulse, l3. .swell .,.,. 'db ""d urea in investigatio• ...t.lbe~tes insipidus (central and nephrogenic and their causes)
in the child. 'Hte child must have norm.:1l adrenal and renal functlt • •Uonir
renal failure (can usually be excluded if there is a normal urea and
FmaHy the ch~ld must not have received loop diu"~ re:ently. • ltirtin&e) and following relief of a chronic obstructive nephropathy
Thus !n questions look for: (a) the plasma osmo!ality; (b) the urinary o:;u polydipsia.
laHty- typically inappropliately high relative ~c h'1e p lasma osmolality.
Under normal circumstances the l!rinary osmolality should be les!> deprivation test
130 mOsmol/kg in the presence of hyponatt<::ania. In SIADH the 1 useful test to distinguish between diabetes insipidus and psychogenic
osmolality is typically higher. You ~ay be asked to interpret such a test in a data question. Here the
Treatment involves fluid resmction to tw~thirds maintenance. The demonstrate an inappropriately dilute urine in the presence of a con-
ma sodium and osmola lity should be measured regularly. as well a:~ I se~. It is potentially a very dangerous procedure and meticulous
quent weighing. If hyponatraemia is causing complications such as sei11 be taken to measuring clinical parameters hoUr-ly (such as weight.
then a quicker return of plasma sodium to normal is required a nd e<m and urine output). The test is carried out until there is a 3% loss in
achieved using intravenous administration of hypertonic saline (3%) At the s tart of the test the patient voids urine; this is discarded and then
190 concurrent furosemid~ (fr usemide) administration if there is also an e l ~ins. After the test the urine and plasma osmolalities are measured. 19:1
In the normal patient fo llo wing water deprivation the urine osmolality Endocrine problems: Cushing, h ypothyroidism , Ma uriac syndrome,
usually > 800 mOsmol/kg- however in a normal patient in whom there
polycystic ovarian disease.
been prolonged polyuria, the urinary osmolality may be as low
-Syndromes: Prader-Willi, Laurence-Moon-Biedl.
600 mOsmol/kg, such as tha~ following chronic psychogenic polydipsia.
- Hypotlurlnmic disordas e.g. post infection or trauma.
diabetes insipidus the urine osmolality is usually < 200 mOsmol!kg. A u
nary concentration> 200 mOsmol/kg makes Dl very unlikely (or may be In babies macrosomia may be caused by· Beckwith-Wiedemann syndrome, m
::::s
sible in a partial defect). DDAVP may be given at the end of the test and lotos syndrome (also macrocephaly, large hands and feet) and having diabetic Q.
cause concentration of the urine in cranial DI and produce no chang~ lllothers. 0
n
nephrogenic 01. In practice a concentrated urine > 800 mOsmol/kg in ::!.
presence of a normal serum osmolality< 290 mOsmoJ/kg excludes DI. ::::s
Jolycystic ovarian disease 0
0
lycystic ovarian disease or (Stein-Leventhal syndrome) presents with obe- cc
hirsutism (sometimes with acne) and irregular periods (also primary or '<
Because of the vast array of clln!cal presentations of anorexia, it comes UJ• amenorrhoea) usually from puberty and the symptoms deteriorate
the examination ·not infrequently. It is about 10 times more common With time. Numerous ovarian cysts are
females, with an average age of onset during adolescence (males mean
seeno n ultraS<.) und. Androgen lc\'els
IR el~vated (SHBG low) and there is a raised LH:FSH ratio with a normal or
12 years;JeiJ1Ctles: 16 years). Psychologically there is a disturbed sense of ~ FSH (tha t is, LH is high). Infertility is a cpmmon problem later on, and
image with a morbid fear of obesity, and relentless pursuit ~f low leatment with clomiphene or wedge resection of the ovary can be effective.
weight. Physically there is a body weight more than 25% below the
weight and there is often amenorrhoea. Additional features are as
evi~ence of vomiting, excessive exercising or laxative abuse; nnrn>r\tror~llll& C".ALCIUM METABOLISM ·· . .
bingeing (bulimia) followed by remorse and efforts to vomit or lose
weight in other ways.
Know about other features that can sometimes cause diagnostic cunru1• - lh plasma 50% of calcium is in the free ionised state, 45% is ~lburnin bound
constipation (very common), hypotension (often postural}, tnd about 5% is complexed with dtrate and phosphate. It is the free ionised
hypothermia, sensitivity to cold, amenorrhoea (may precede weight !Qto lcium that .is biologically active. Distribution between these various forms
25% of cases), hypoglycaemia, alope(:ia (sparing axillary and pubic h~ll II affected by: (a) pH - increased acidity displaces calcium from albumin
hypopituitarism), lanugo hair on the trunk and extremities, ankle i-creasing ionised calcium; (b) increased serum albumin increases serum total
leucopenia, vomiting and purgation may cause hypokalaerrua, alkalosi81 eaJcium; (c) precipitation in diseases (e.g." pancreatitis) can lower serum calcium;
diac arrhythmias, dental erosions and knuckle calluses (Russell sign) {ct) alterations in bone turnover. Laborato ries measure total calcium.
tooth decay (as a result of self-induced vomiting). I:Prrected calcium may be useful to see if the apparent hypercalcaemia might
!.f caused by increased albumin concentration (or vice versa). It can be calcu-
Hormonal changes in anorexia ..ted as fo llows.

-Decreased: LSH, FSH, testosterone, oestradiol, T3 and T4. If the albumin level is more than 40 g/1 (e.g. 45) then (45- 40) x 0.02 =0.1,
-Increased: prolactin, growth hormone and cortisol. which is then subtracted from the total calcium concentration.
- Differentilll diagnosis includes: thyrotoxicosis (especially in a slide of 11 If the albumin concentration is less than 40 g/1 (e.g. 35) then (40 - 35) x 0.02
face), diabetes mellitus, neoplasia, malabsorption, inflammatory bow ""0.1, which is then added to the calcium concentration.
disease and hypopituitarism.
ium concentration in the blood is mainly controlled by two hormones:
One-third recovei" fully, one-third partially recover and in one-third it 0 and parathyroid hormone (PTH). Increased ionised calcium
a severe chronic disease. Poor prognosis is associated with male sex, lah•t ration inhibits PTH release whilst low serum calcium concentra-
of onset, bulimia, purgation, 1.1nstable family relationships and the greot•• have the reverse effect. Calcitonin is released from the C cells in the
weight loss. · -tu.-.... irl gland in response to hypercalcaemia but physiologically has little

D
When faced with an obese child you must always have a list of se<;1
main effect is an increase in calcium and increase in phosphate.
192 causes to exclude.
lecalcife rol (vitamin 03) is derived from the diet or from the UV light
193
conversion of 7 dehydrocholesterol. This is hydroxylated in the liver to 25-0H IJDaptoms . .
cholecalciferol (by th~ 25 hydroxylase enzyme) which is then hydroxylated in Mwicle weakness, tetany and cramps (Trousseau's sign- carpopeda~ sp~m,
the kidneys (by 1-alpha hydroxylase enzyme) to 1,25 dihydroxycholecalciferol Chvostek sign - tap over parotid gland causes facial muscle tw1tc~g).
(the biologically acth·e form). lllmember that tetany can also occur with a normal calcium und~r cond1~
-Gut effect: increases calcium and phosphate reabsorption IIalkalosis (because of decreased biologically active ionised calcJum), stridor,
-&me effect: stimulates osteoclast resorption. para~thesiae and numbness, cataracts, short stature and behavioural
Changes.
-~ Parathyroid hormone
Its main e1fect is an increase in calcium and decrease in phosphate levels. 11 HAEOCHROMOCYTOMA
·~
::s - Bone effect: rapid release from bone, increased osteoclast resorption Phaeochromocytomas may come up in a grey case. They are ca~echolam~e
(f) (longer effect} llcreting tumours of neuroectodermal tissue. Ten per cent are ~tlateral, 10 :to
c( - Renal effect: increased calcium reabsorption, decreased phosphate Dlignant and 10% extra-adrenal. Ten per cent are associated wtth other syn-
reabsorption, stimulation of the 1-alpha hydroxylase enzyme. dromes, for instance neurofibromatosis or type n MEN. The adrenal tumours
E ft\Ainly secrete adrenaline and extra-adrenal tumours main~y secrete ~ora­
cu
>< dml<lline. Clinical features include: hypertension (50% sustam~, 50% m_ter-
w Hypercalcaemia
11\lttent), weight loss, headaches, chest pain, attacks of sweating, fl~s~g,

-
u
'i:
.~
"C
Q)
cu
Causes
Primary hyperparathyroidism (85% adenoma, 15% hyperplasia), hyperalbu·
minaemia (however if corrected ~s above calcium will be in the normal
range), chronic renal failure with tertiary hyperparathyroidism, milk-alkali
'-chycardia and palpitations, polyuria and nocturia, artd glycosuna. w tth
Impaired gfucose tolerance. In addition anxiety, nausea and behavtour~l
changes may occur. In chronic situations a blunting of the normal sympathetic
IISponse may be seen with ·postural hypotension. Paroxysms usually last
c.. syndrome, vitamin D excess, thiazide diuretics, sarcoidosis, tuberculosis, 15-45 min.
neonatal hypercalcaemia (secondary to maternal hypoparathyroidism}, thy· Investigations: 24 h urinary analysis for catecholamine by-products
rotoxicosis, Addison disease, factitious (with venous stasis on blood taking). (metanephrines: vMA - vanillylmandelic acid; HMMA - h~droxyf!!ethoxy­
mandelic acid). False positives are seen in stress; illness; caffeme, b~nas and
Symptoms vanilla consumption; beta-blockers and others. Plasma cat~ol~es, Cf
Anorexia, nausea, vomiting, abdominal pain, constipation, rarely peptic lean and MrBG scan. Beta-blockers may result in a paracioXJcal nse m blood
ulceration and pancreatitis, polyuria, polydipsia (acquired nephrogenic dia· pressure. Surgery cures in 75% of cases and is carried out with alpha- and
betes insipidus), muscle weakness, depression and poor concentration beta-blockade.
Hyperparathyroidism is more likely to present with renal s tones (nephrocal· Neuroblastomas may also secrete catecholamine but to a much lesser
cinosis), peptic ulceration, pancreatitis and chondrocakinosis as compared to txtent.
hypercalcaemia from other causes.

Hypocalcaemia
A rare syndrome which is caused by a tumour of the argen~ ~ells in the
Causes ,Ileum, appendix or bronchi. lleal carcinoids readily metastastse w~ile th~ oth-
Hypo~lbuminae~ia (if corrected however calcium will be in normal range)1 ers rare ly metastasise. The tumour produces 5Hf but th•s wlll be
chrome renal fa~ure, acute pancreatitis, prematurity, vitamin D deficiency, metabolised by the liver (in the case of a gastrointestinal carcinoid) unless
hypoma~esaerrua (Mg needed for PTH activity), hypoparathyroidism (usu hepatic m etastases are present in which case 5Hr enters the systemic circu-
ally aut01mmune but also parathyroid agenesis in DiGeorge syndrome and "' lation. Extraintestinal carcinoids secrete 5HT .directly into the systemic
a complication of thyroidectomy) and pseudohypoparaJbyroidism (hereditary circulation. Typical attacks include paroxysms of facial flushing, bronchocon-
end-<:>rgan resistance to PTH: affecting males more commonly, PTH levels art 'ltriction causing dyspn~a; fever, nausea, vomiting, abdominal colic and
very high, and they have a characteristic phenotype with short stature, moon watery diarrhoea. ln addition features of the primary tumour itself may be
face, mental retardation; calcified basal gang.lia and short fourth metacarpnl present, such as gastrointestinal obstruction. Chronic ~UC:inoid. syn~me
bone). In hypoparathyroidism if i.v. PTH is infused there will be an increase In may result in pulmonary stenosis and tricuspid regurgitation (nght s tde of
urinary cyclic AMP but there is no response in pseudohypoparathyroidism. h1 heart).
pseudopseu~o~ypopara~yroidism there is a similar phenotype to pseudohy Investigate with 24 h urinary collection for 5 hydr0xyindole acetic acid
194 poparathyrotdiSm but patients have normal biochemistry. (5HIAA). 195
lhlft gradually lower your fmger watching for lid lag: that is, the upper eye
MULTIPLE ENDOCRINE NEOPLASIA (MEN) -~:,._.: ·..; ''· ,t~
coming down after the eyeballs do.
These are familial disorders inherited in an autosomal dominant fashion.
They describe tumours which may be benign or malignant, or hyperplasia IMv examine the neck from behind feeling for a goitre. Ask the child to
developing in more than one endocrine gland. It is important to recognise wallow and feel for any movement in any masses felt (indicative of thy- m
these rare syndromes since the presence of <?ne endocrinopathy might lead 'ltdal origin). Ask the child to stick out his tongue. Any moveme~t of a ::::J
0.
you to look for other features common to the MEN syndromes, especially if INcture on protruding the tongue could be caused by a remnant m the 0
there is a family history. They are listed in decreasing order of occurrence. lftJroglossal tract (e.g. thyroglossal cyst). Percuss over ~e upper sternum n
"a large goitre is present to check for retrostemal exte,nslOn. :::!.
c; ::::J
0
.~ ~-ultate the thyroid gland for bruits fda goitre is present).
~
~1 0
blmine all the lymph nodes in the cervical region.
c.o
::::J - Pa~thyroid adenoma/hyperplasia '<
en - Anterior pituitary adenomas, e.g. prolactinomas, GH secreting tumours l.ook at the legs for necrobiosis and pretibial myxoedema.
ct
.. - Pancreatic islet cell secreting tumours, e.g. secreting insulin, glucagon, gas·
Now examine the reflexes which are increased in hyperthyroidism and
E trinoma, VIP
~h in hypothyroidism. Get the child to kneel on a chair _and test the
co
)( - Adrenal cortical non-functioning adenoma
w -Thyroid follicular cell adenoma. lftlde reflexes. In hypothyroidism there will be a slow relaxation phase of

-
0
·a:
.!
"C
G)
co
~pe2(a)

-Thyroid medullary cell carcinoma (secreting calcitonin)


1M ankle jerks.
Alk the child to speak in order to hear the hoarse voice of hypothyroidism.
'lnally offer tO plot the child's height and weight on growth charts.

a. - Adrenal medulla phaeochromocytoma


-Parathyroid hyperplasia or adeno~.
a list of things that you would look for routi.nely in a diabetic child.
Type 2(b) 'Wbu should first of all carry out a general observation looking for obesity,
As for type 2(a) plus marfanoid appearance, perioral mucosal adenomas and 11\lnness, well· looking or not well looking.
visceral ganglioneuromas. You should examine injection sites making sure that there is no lipoatro-
,t.y or lipohypertrophy. Look also for ~e pr~ence of skin prick test sites
tlftciicating that the child has been checkmg his blood glucose).
The only endocrine abnormality that you are likely to be asked to assess in the Get the child to perform the 'prayer · sign' with his hands to demonstrate
clinical examination is the thyroid status of the child. diabetic sclerodactyly (see earlier in chapter).
-Firstly obserVe the child. See if there is anything immediately obvious (e.g. Offer to examine the blood pressure and perform a fundoscopy despite the
is he thin, proptosis). You may ask the child to look at the ceiling to make 11ct that such end-{)rgan damage is extremely unlikely in the childhood
a goitre more obvious. Are there any scars present from previous thyroid fOPulation.
surgery?
Rl\ally offer to plot the height and weight on a growth.chart and test the
-Take the child's hands and feel them. In hyperthyroidism they will be ll'lne with a dipstick and test for microalbuminuria.
warm and sweaty whereas in hypothyroid~m they will be cold and dry.
Ask the child to hold his hands out in front of him (dorsal sides upwards)
with outstretched arms and fingers widely spaced. Now place a piei:e of
paper on the hands to demonstrate the fine tremor of hyperthyroidism.
- Now take the pulse, feeling for the tachycardia (and frequent ectopic beats)
of hyperthyroidism or the bradycardia of hypothyroidism.
- Look at the eyes for proptosis and test for lid lag. This is done by asking
l96 the child to look a t your finger as you raise it above his field of vision and 197
aematology
8
tology is a frequent topic for questions in the MRCPCH examination.

NAEMIA · · · . · .,: ·.· . · · ·· .


Important that you have a thorough understanding of the pathophysiol-
11\d classification of anaemia since this will give you a framework for dis-
g many other haematological disorders.

moglobin production in the fetus usually starts by the third week of


tion, primarily in the yolk sac. By month 3--4 of fetal life the liver and ·
1t1n take over erythropoiesis and finally by m onth 6-7 the bone marrow
es the principal production site of blood. At birth haematopoiesis
urs in all the bones but thjs gradually reduces during cruldhood so that the
I bones are mainly involved as the child ages (vertebrae, ribs, sternum
lvis) and the long bones play less of a role in blood production.
The no rmal values for haemoglobin concentration change during the first
of life and it is important to be aware of these changes since it can avoid
gnosis and unnecessary investigation in some cases (see Table 8.1).
m babies are relatively polycythaemic; the haemoglobin concentration
110 its lowest levels by 2-3 months (physiological anaemia) and then slowly
again. Low haemoglobin concentrations at 6 months may be caused by
• nd folate deficiency especially in premature babies.
1ft the fetus !'aemoglobin is in the form of fetal haemoglobin (HbF, consisting
IWo alpha chains and two gamma chains) but towards the end of gestation the
begins to produce beta globin chains as well so that by birth the baby has
HbA (adult haemoglobin- two alpha chains and two beta chains) ancJ 80%
haemoglobin. Fetal haemoglobin has an oxygen dissociation curve to lhe
that is, it has a very high affinity for oxygen but is less good at giving it up.
was ideally suited to intrau~erine life. The average child has haemoglobin
Is made up of 95% HbA (adult haemoglobin) and the remainder HbF
W'Yo and HbA2 2-3% (two alpha chains and two lambda chains). The rapid
in Pa02 at birth causes a reduction in the production of erythropoietin 199
Decreased production
-Reduced haematinics (iron, folate and B12)
Table 8.1 Variation in haematological indices during the f"ltSt year of life
- Infiltration
Haemoglobin values White cell
(mean) gldl MCV (mean) fl count (x 10'11)" -Aplasia
-Chronic disease.
Term newborn 19 108 5-25
2 months old 11 100 6-15
1 year 12 86 6-15 Ina-eased loss
·Neutrophil$ (N) predominate at binh compared to lymphoc:ytAIS OJ (~:30% N."l) but this - Haemorrhage
ratio is reversed by 6 months of '9e and this is maintained for the fint ._5 Yf!<SI"S but Is - Haemolysis:
reversed yet again by puberty (SS%:40% N:l).
a. Intrinsic (membrane defects, haemoglobinopathies, red cell enzyme
defects)
b. Extrinsic (microangiopathic haemolysis, immunological).
which results in greatly reduced red cell production for several weeks.
results in a decrea~ in haemoglobin concentration by about 2 months of Another way of classifying anaemias is to distinguish between microcytic,
(physiological anaemia) and this value is usually not less than 10 g/dl in 1M)rmocrtic and macrocytic causes of anaemia.
children, and usually well tolerated by the infants; this fall in 1. Microcytic: Iron deficiency; beta thalassaemia trait, sideroblastic anaemia,
however more dramatic and occurs earlier in premature babies. This chronic disease (usually normocytic) and lead poisoning.
in haemoglobin is partly compensated for by the increase in HbA which
oxygen dissociation curve to the right and thus gives up oxygen more .....~•-,- Normocytit;: Bleeding (acutely), chronic disease, haemolysis.
The reduction in Hb results in increased erythropoietin production as a Mllcrocytic: Megaloblastic anaemia (B12;. folate), liver disease, myelodys-
reduced tissue oxygenation (negative feedback loop) so that haemoglobin plasia, hypothyroidism, aplastic anaemia, reticulocytosis, chronic alcohol
begin to rise again with an appropriate reticulocytosis (not to be confused tngesti~n, newborn and pregnancy.
haemolysis). The normal blood volume in a child is 85 ml/kg.

Life cycle of red cell ·•DOct-1rurn abnormalities


Bone marrow pronormoblast ~ normoblast ~ 'reticulocyte (1 day In ••M.albu will ,face questions that will ask you to interpret blood indices or films
marrow and then released into peripheral blood with a survival of 1 (I you should be familiar with the commoner blood-film abnormalities.
the peripheral blood) ~ mature re4 cell.

Reticulocytes contain excess membrane or insufficient haemoglobin and are recog-


These are an important indicator of: (a) bone marrow response to as 'target-like' with red peripheries, central pallor and with a dot of
(increased in haemolysis and decreased in haematinic or aplastic ~~~t~mo,gJ<>bin at the centre.
and (b) successful response to treatment. A reticulocytosis gives th
film increased staining called polychromasia. The presence of
penia in the presence of anaemia implies: (a) that there is an ah'no1mu•11
the level of the bone marrow; (b) the picture seen is so shortly II
episode causing the anaemia that the bone marrow has not had
respond, for example a large haemorrhage, or (c) that the reticulO\
being destroyed, possibly by an immune-mediated mechanism.
Reticulocytosis is seen in:
-Haemolytic anaemia
- Acute severe bleeding
- Beginning of a remission in aplasia
- Response to treatment in haematinic deficiency.
bodies
nuclear round remnants found within erythrocytes. Remnants of DNA
Classification of anaemias
RNA. 201
~fJ!) It I~ important to have a system in your mind.
- Beta thalassaemia Combination of iron deficiency with a BIZ/folate deficiency
- Post splenectomy Iron deficiency anaemia (with microcytosis) and havi<"lg received a blood
- Megaloblastic anaemia transfusion.
- Sometimes found in premature infants.
10philic stippling
Poikilocytosis ns numerous small dol'<: irt the 1~ cell d ue ~o alph;;?, chain dumping.
Variation in shape of erythrocytes.
-Severe iron deficiency
- Bet~ thalassaemia
-Tear drop poikilocytosis (seen in myeloproliferative disease/other bone
marrow infiltrath·e conditions).
esplenectomy features
Howell-Jo!ly bodies (spleen u.ii-uallY involved in removal of excess cell
ltmnants}
Heinz bodies
Acanthocytes (red cells with spiny projections protruding from the surface,
Denatured haemoglobin/haemoglobin remnant - stained by supravital stain·
ing- seen as a dark dot in erythrocyte.
IIIIo seen in abetalipoproteinaemia)
Target cells ·
- Red cell enzyme defects (e.g. G6PD deficiency, pyru~·ate kinase lchisto..'"}'tes (portions of disrupted cells).
deficiency)
- Drugs and chemicals causing haemolytic anaemia. ~~~~IIDe~rvthnlblastic pi~
·~--.... in numbers of primitive .cells in the blood film, for exmnple nudeat-
Left shift and leukaemoid reactions ccl.ls (nonnoblasts), xnyelc:.~ lasts.
Less mature white cells released prematurely from the bone marrow. Careful
examination may be needed to distinguish from leukaemia. Also refers to lflligna..Y'\t infiltration of l:he bon~ marrow
increased neutrophil/lymphocyte ratio. Mfcoba<;rerium, e.g. TB infection
Marble bon: disease (ostoopetrosis)
-Sepsis (caused by increased demand on neutrophils; less mature cells arc Mye\ornatosis
released prematurely), tuberculosis, syphilis, toxoplasmosis IIJelofibrosis.
- Down syndrome.

Rouleaux formation
Erythrocytes stacked in rows one on another.
--Inflammation •111(x:x1 film may be giv~, ~ l.n yo~.:1 in the form of a slide or described to !ou
- Malignancy. •1nuata or grey case question.

Spherocytes
Seen as spherical cells with no central pallor; give rise to a low MCV.
•ttn•in feature is of sph':tocyi-es; which compared to nonnal red cells are
- Hereditary spherocytosis instead of biconcave, and thus lack. th~ir cf..aracteristic central pallor.
-Immune haemolytic anaemia -.lnrtrtndc. is often prominent. Oo not forget that if a sple:;"lect.omy has been
- Severe burns •lrllned then h>..atures of post spltenectomy may also be prec.,ent (sile above).
- Post transfusion.

Dimorphic blood film -lha~;ills~~erraia majow-


The presence of two differently sized populations of red cells, with increa • hypochromic ariaemin (jpale spar.se small red cells on blood film),
red cell distribution width CROW). anisogttosis ('1-'ariation in s;ize of the red ce11s), poikilocytosi$ (varia-
- Sideroblastic anaemia (bone marrow cells unable to utilise iron to f0111 basophilic stippling {dumped togeth~r alpha chains}, ~rget
haemoglobin characterised by ring sideroblasts in bone marrow: caused I• red cell fragmen~ As a ~suit of bo.ne·n,arrow stimulation t.h ere may
202 inherited and acquired causes such as lead poisoning, anti-TB drugs) Increased nucleated red cell!s, white cells and platelets; howevP.r white 203
Haemolytic uraemic syndrome
cells and platelets may be redu"ced if there is concurrent splenomegaly caus . . . . .
·mg h ypersp1erusm.
· This is an ellample of a mtcroangtopathu: haem"'' nc andt:mta and the blood
film can be identified by hvpochn:~mta . fralo;Oit:ntt-d red cells. Burr cells
lSChistocvtesl and a stgnifkant paucttv 10 plah•lt>ts lt L'> cau~ by t>liU!ssive
Sickle cell disease
"hearing ot the red \ells Microant<"'pathtc h.u?molvtt.: an~emia mcty also
The characteristic feature is of sickling of the red cells. In addition there ma occur in children with pr~thetic \'ah c!S, disSt:mm.ttt!d intrnascular ...oagv-
be hy}X>Chromic, microcytic cells, numerous ta~t cells, polychromasia ~ lattqn, thmmbotic throm.t-~~l~>pcnl' Furpura h.tefl'<'ngiomas anJ an ~mt>
numerous nucleated red cells. The presence of Howell-Jolly bOdies will indl 0\cllignancies. ·
cate splenic function in the child (most children are fwlctionally asplenic b y
year of age as a result of repeated splenic infarction).
HAEMOLYSIS
Malaria Haemolvtit· disorders are dh·idt.-d up into tho~ which produce extravascular
ha~mol~sis !the majontv} where reti ~ells c!re TLmc\'E'd mamly by th.o spleen
A common s lide question is the erythrocyte with a ring form within it. ~ lt!ading. tc splenomegaly it haemolysas lS t:hl\~l'K !r-h,,v::l~ular haemolysis
Plasmodium folciparum there are thin small rings, in P. ovale there are Jar~ occurs when red ceUs are r~padl ~ lysed withiJ~ the vasculature with some
coarse rings each with a single chromatin dot, and in P. viva:r the re is a la r haemoglobi.'1 being lost in the urine as haemoglot-inuria.
ring form with a single chromatin dot.

The consequences of haemolysis


Iron deficiency anaemia
Anaemia (no·rmocytic, normochromic), unconjugatf'd hyperbilirubinaemio,
Hypochromic microcytic anaemia (hypochromia descn'bes when the peri
ancreased unnary urobilinogen, h.'lemoglobinuria (in intravascular haeml"):y-
eral pink haemoglobin rim of the red cell is less than tw~thirds of the dia
lls), decreased serum haptoglobin since it binds to released haemoglobin (NB
e ter of the entire red cell). Anisocytosis, poikilocytosis, targ~t cells and cig
hap toglobin .is absent in newborns and may ·be congenitally absent}.
cells /pencil cells may also be seen. Differential diagnqsis of the microcy
Reticulocytosis, Polychromasia, fragmented red cells and spherocytes (if
hypochromic anaemia includes beta thalassaemia trait, chronic ii).flammati
hereditary spherocytosis or a4toimmune). No urinary bilirubin (acholuric
and s ideroblastic anaemia. Lead poisoning also gives rise to a fnicrocy
jAundice). Bone marrow erythroid hype rplasia, extramedullary
.hypochromic anaemia but one would also expect to .see basophilic stipplinf
haematopoiesis. 51 chromium labelled red cells can be used to look at red cell
•urvh·al which is reduced in haemolysis
Megalobl~c anaemia
The red cells are large (macrocytic) ~ith anisocytosis. Neutrophils are la Common haemolytic questions
than normal and a have characteristic hypersegmented nucleus (neutrop
usually have up to five lobes in the nucleus but in megaloblastic anaemia tl I. A 3-year-old Caucasian child is noted to be pale an<:1 slight.Lf jaundiced. She
number is greater). This is sometimes called right shift and is also seen has recently had a viral URTI and jUst has a residual rough. On examina-
uraemia and hepatic disease. Leucopenia and thrombocytopenia sim tion she is notE'd to haw an enl.lrged spleen and is otherwise well.
reflect ineffective haematopoiesis. The bone manow is hypercellular 'W Hb Q.Sg/dl
megaJoblasts with nuclear I cytoplasmic dissociation. wee f,Q
Platelets 12Q
Lea"d poisoning l'nwnjugated bilirubin 'n J,lmolt l
OCT negative
-Microcytic hypochromic anaemia
81~ film num·~mus sphen'ICytes
- Basophilic stippling
Reticulocytes ++
-Evidence of haemolytic anaemia.
this story is typical of hereditary spherocytosis. It has a mainly AD inher-
Jnfectious mononucleosis !1-nce but is sporadic in 20"~. of cases. It is caused by a mutation in the spec-
In protein (a membrant> skeletal protein) leading to membrane fragility
1}Us is characterised by a lymphocytosis and the presence of atypical h d the red cells are remm:ed by the spleen. Symptoms may include those
phocytes which are typically amoeboid in appearance, have a large nu< used by anctemia and intermittent jaundice which may be precipitated by
:204 and abundan~ cytoplasm. 205
nra~ Illnesses. Chronic hc\emolysis mc\y result in gallstones Sudden reduc· old antibody AlHA produces lgM autoantibodies which agglutinate red
tion i~ Hb concentration may be the result of abrupt haemolvsis or infec- at lower temperatures(< 37.C). In children it usually fol-
tion ~ith hum~n eryt.hrovirus (formerly pan:ovirus) infection causing M lnfect:ior\S such as mycoplasma and infectious mononucleosis but is also
aplastiC anaemia cwh1ch may also occur in sickle cell disease ). NB SLE and some lymphomas. OAT IgM is positive (with lgM often
Hereditary spherocytosis is difficult to diagnose during an aplastic crisis. It against the I antigen of erythrocytes) and anti-C3d is positive (detects
Q) X
"C may present in the neonatal period with jaundice ~ the first dav of lift> • ller:nettt components). Haemolysis tends to be milder than warm AIHA. D)
(50% of cases). Because of the presence of spherocytes both in he~itarv •tne~rtt involves a,·oidance of the cold, immunosuppressives, warmed CD

-
:::::1
(!)
spherocytosis and ABO incompatibilitv the two mav be difficult to dis~· baflSfusion; splenectomv is of no ~-
3D)
ca guish from each other as a cause of ~eonatal jau~dice. Splenomegalv i:. may be given a questi~n with the rare condition of paroxys~l cold 0
> ..:ommon (80% of cases). · It is classically associated with congenital or acquired 0
·~ cc
:::::1
lm·~sti,f{ntions: These include: FBC (anaemia with reduced !\ltCV), blOod but more commonly follows viral illnt!SSes such as chickenpox,
"<
U) film. red cell fragility test (increased red cell lysis in hypotonic solutions and especially gastroenteritis. Here haemoglobinuria occurs after
< compared to normal red cells-). There is an increased ROW. Treatment con·
sists of splenectomy (to reduce haemolysis and possibility of traumatk
to the cold. The IgG binds to red cells in the cooler parts of the body
-aa.....,.;f:i,.... , for the P antigen) and t11en when it reaches the warmer parts
E
ca rupture) in many cases unless haemolysis is mild or the spleen is only iated haemolysis. Investigation involves use of the
>< mildly enlarged. This is delayed until after 5 years of age because of the biphasic lysis test. Treatment involves avoidance of the
w risk of O\~erwhelming sepsis. In view of this the folJowing precautions arc

-(.)
possibly immunosuppressive agents.
·.: taken pnor to splenectomy: Pneumovax, Hib vaccine and prophvlactlt causes of haemoglobinuria include the causes of intravascular
penicillin. . · (especially if acute~ sud'\ as microangiopathic haemolvtic
.~
"C for example HUS and paroxysmal nocturnal haemoglobinuria.(an
Cl) 2. A 7-~ear-old child presents with lethargy and is described by the parentl seflSitivity of a done of red cells to lysis by complement) and infec-
ca as bemg paler than usual. The child had had a bad flu 2 months ago which as malaria (blackwater fever),
c..
was slow to resolve and the symptoms of tiredness had reallv started sincr
then. On examination the sclera are slightly yellow and a ~ld degree Ol • Greek boy is seen in the .A&E department of his local hospital
splenomegaly was found. Blood results were as follows: _generally unwell. According . to his mother, he has been passing
unne for the last couple of days. On routine questioning of the mother
Hb 5.-1 g/ dl (normocvtic, normochromic) the possibility of ingesting any medicatiof\S she replied that there
wee 7 .
a small posstbility. She had com.e into his room a couple of days ago
Platelets 208· removed a container of tablets from him. He had removed the con-
t.:nconjugated bilirubin 61 ~mol/1 from the suitcase that they were in the process of unpacking (they
OCT positiw (anti-lgGl Just returned from their holiday iin Kenya), but she was sure that there
Blood film anisocytosis, polychromasia, no tablets missing.
reticulocytosis, spherocytosis
6.7g/dl
The picture here describes an autoimmune hae~olytic anaemia. The ntll 15.0
mochromic normocytic anaemia with a positive Coombs' with lgG coatln~ 239
~he red cells and spherocytosis make the likely diagnosis a warm antibOil, 9%
autoi~mune haemolytic anaemia (1~ .a ntibodies agglutinate red cell& p•1 1 Fragmen\ted red blood cells, Heinz bodies.
erenhally at warm tempt?ratures > 3TC). This form is mainly idiopathl bite cell§ (bite cells are cells that look as if a
(60"'<>) and associated with thrombocytopenia fnot in this case) in 20".. 1•1 bite has· been taken out of them. possibly
cases (Evan syndrome}. The remaining -ltr.<> of cases are the result ol 111• because 1of Heinz body removal by the spleen:
u~derlyin~. disorder such as an auto1mmune disorder, for example rheuutA also call~ blister cells)
tOld. a.rt~nhs. SLE. lymphoma nr other ~alignancy and drugs (methylclo1••
pemc1lhn}. Red cells are coated by IgG immunoglobulins giving a posit is glucose-6-phosphate d-ehydrogenase deficiencv CG6PD deft-
DAT. Treatment consists of steroids which reduces the interaction b etw1 ... The child had swallowed' se\·e!f'al primaquine tablets. ·It is the com-
macr~phages and coa.ted red cells. lf no improvement consider immunO'illl red cell enzyme deficiency. It is iinherited in a sex-linked fashion with .
presswcs such as azathioprine. If the condition becomes chronic con!llt Female carriers may ~xhibit som.e milder features (as in
splenectomy which has a success rate of about 60-70%. Blood trans fu h muscul_ar ~ystrophy as a restult of random lyonisation). It may be
206 should be avoided. by oxidab..·e stress. stress off any sort or infection. It is common in 207
American blacks (10%), and Mediterranean peoples (such as Italians, Aral•
and Greeks) as well as in South-East Asians. It affects the hexose monophQi t4.,_.- - - - - - - - -- - - - -- - - - - - - - - - -- -
phate pathway (within which G6PD holds a vital role) which produces redu :~======~~~~~~~~=~=j~~~~~~~r==
ing powe~ for the red cell in the form of NADPH (which maintains gl~
tathione in a reduced state). Reduced glutathione is important in cmnoiilt\Jl
Cl)
oxidative stress to the red cell. Absence of reduced glutath.ion~ll result COE/cde. Rhesus relates
:5! cross-linking of spectrin (leading to red cell rigidity) and haemoglobin oxidl to 0/d. Rhesus ...,e (83%),
:::s
(!) tion to methaemoglobin with Heinz bo<fY precipitation in the cell. Both Rhews -ve (17%)
these effects will result in haemolysis. . ~~~~~:::::..- Present. A • Antt-8. None present
~ Normal enzyme variants are G6PD type B (found in most whites ::':::: B • Anti-A. 0 • Anti-A.&".- - - -
·~ 70% of American blacks) and type A+, another normal variant (found A8 =nil
:::s approximately 10-20% of American blacks). Abnormal variants · Possible in the first After the first pregnancy

"'
<( variant A- seen in Afro-Caribbeans which becomes more unstable
degrades as the cell ages (thus reticulocytes have adequate levels, and Mi
pregnancy (only if anti-A
or anti·B antibodies are
lgG class; approximately'
E haemolytic crisis is usually self-limiting, resolving when a new uuvu1""' 10% of

w
"'
>< of red cells is formed). This form tends to be very sensitive to ""'' u" '"•
stress and precipitated by drugs such as sulphonamides and p
Strongly positive

...
0
'i::
.!
G6PD-Caucas ian/Mediterranean yariants are seen in Mediterranean
pies who tend to be particularly sensitive to fava beans. They tend to
fer from chronic haemolysis and acute life-threatening haemolytic
"C Usually more severe than
Cl) G6PD-Canton variants are especially prone to haemolysis in the ABO Incompatibility
"'
a. period. There is of course overlap between all the groups. G6PD
to protect aga inst malaria. Intravascular haemolysis is common
haemolytic crises causing haemoglobinuria and jaundice. The blood
as above.
Diagnosis is made by family history, history of oxidative stress and by
forming an assay for G6PD enzyme. Remember to repeat this test if it is questions relate to haemoglobin electrophoresis. It is important that you
mal during a crisis since rapid production of reticulocytes (with some _o f the uses and are able to interpret results frOm them. This is the
enzyme levels) and loss of the mature enzyme deficient cells may most important investigation in the diagnosis of haemoglobinopathies.
give false negative results. may-give you percentages or give you a diagram of a haemo-
Treatment is supportive with treatment of infection, removal of elecfrophoresis. 1his is usually in the form of a copied diagram or a
drugs and blood transfusion. Splenectomy is usually of no use. In ca of the actual electrophoresis. Either way the bands are labelled with the
chronic haemolysis folic acid and vitamin E are sometimes given. botdOlbin type and the .width of the band corresponds to the proportion of
Pyruvate kinase deficiency is the second most common enzyme l*moglobin type that makes up the haemoglobin being tested.
(glycolytic pathway) inherited in AR fashion . It is also exacerbated by child: HbA 95%
or infection. HbA2 2-3.5%
HbF 0.5%
HbA 20%, HbF 80"/o. Charts are available to determine the normal
Many questions relate to ABO and Rhesus haemolytic disease (see TabI of.aifferent Hb types at different ages. The following are examples of
The Kleihalier test is an acid elution test on maternal 'ttlood and rcll results seen in children.
the fact that HbF in the fi!tal cells is acid resistant {compared with ml\l•t
cells) so that fetal cells remain pink and maternal cells become colo111
The percentage of the fetal red cells in the maternal blood is then ctlh
ed and is a measure of extent of fetomatemal haemorrhage. This cell disease: Note no HbA and high proportion of HbF.
used by obste tricians to determine the dose of anti-0 prophylaxis
HbS 90%
Rhesus - ve women) to prevent rhesus haemolytic disease in ... un,., ...,.
HbF 10%
pregnancies. HbA2 2%
208
HbA 0%
gnte deldions: HbH disease. Anaemia (variable), splenomegaly.
2 .. Sickle cell trait: Note no HbF.
gmt deletio11s: No alpha chain synthesis. Four gamma chains are
HbS 40-45% produced leading to Hb Barts- this is commoner in South-East Asia
HBA 50-55% and a common cause of stillbirth.
HbA2 2%
l lectrophoresis will show varying degrees of HbH and Hb Barts in type 3,
Q) HbF 0%
"C and in type 4 gene deletions mainly Hb Barts.
:::s 3. Sickle cell tr thalassaemia: This and SO thalassaemia have many clini If a child is being investigated for a microcytic anaemia, and iron studies
(!) features in common with siclde cell disease but are generally less severe 11\d Hb elec.gophoresis are n&.rmal but you still think .!flere is a likelihood of
1 haemoglobinopathy, then consider alpha 'thalassaemia. It is diagnosed by
~ HbS 65%
tpecific genetic tests.
·~ HbA 15% HPFH (hereditary persistence of fetal haemoglobin) is associated with a
:::s HbF 10%
U) normal prognosis.
HbA2 3%
< 4. Sickle cell 8° thalassaemia: Note no HbA cf. sickle cell s· thalassaemia. IRON DEFICIENCY ANAEMIA
E
ns HbS 75% Many questions are centred around iron deficiency anaemia. In a child who
>< HbF 15% has an anaemia with a low MCV it is important to d istinguish between iron
w

-
0
•t:
.~
"C
Q)
ns
HbA2
HbA
3%
0%
5. Sickle SC disease: Symptoms similar to sickle cell disease but less seven
HbS 50%
deficiency anaemia and other microcytic causes such as thalassaemia, chron-
Ic Clisease and lead poisoning. This is done with iron studies (see Table 83),
Hb electrophoresis, possibly ESR and lead studies depending on clinical sus-
picion- The blood film is described above and examination of the bone mar-
row would show erythroid hyperplasia and a lack of stainable iron. Iron defi-
c.. HbC 50% Ciency anaemia is common towards the end of the first year of life because of
IncreaSed demands of the body and maternal stores running out. It is more
NB The f9llowing may come in useful in some questions. In sickle cell
common in bottle-fed babies than in breast-fed babies because of reduced
ease the MCV is normal so that if there is a question that has a h igh prop
lbsorbable iron. It may alsO be caused by prolonged breast feeding without
tion of HbS with a microcytic anaemia consider a Hb sickle/thalassae
lrltroduction of sufficient ~lids. Doorstep cow's milk given before the age of
variant (above).
I year can cause GI bleeding. Iron stores at birth last for 5-6 months by which
ltme solids have usually been introduced. Poor diet is the commonest cause
Thalassaemia of iron deficiency and presents most commonly towards the end of the first
year (earlier in premature babies). Premature and low birth weight infants
· 1. Beta thalassaemia major (note very high levels of HbF).
lhould receive iron supplements for at least the first year.
Hb F up to 90% (usually around 75%) Remember the slide of koilonychia (spoon-shaped nails) associated with
HbA2 increased but variable between 3.5 and 8.0% Iron deficiency anaemia. In case histories also remember that iron deficiency
HbAabsent a
associated with pica and brittle hair. Iron in the body is stored mainly in the
2. Beta thalassaemia minor (note raised HbA2).
bm of ferritin (soluble) and is found chiefly in the bone marrow. It is in equi-
bbrium with the cell ferritin so that serum ferritin gives an indication of the
HbA2 us ually 4-7"'o
HbF variably increased (1-3%) but not as high as I ,...,._ 8.3 Differentiating the.:~ of~ mi~c ~ia based on iron.
thalassaemia major .audies
HbA rest Serum Fe TIBC % Saturation Ferritin
lion defldency Low High Approx. 10% Low
Alpha thalassaemia ~~ Low Low Normal Normal«
fib rwefy less inaeased
The alpha chain is encoded by four genes on chromosome 16. Clinical ~11 then 9g/dl)
quences arise with deletion of these genes. leta thalassaemia Normal or ·Normal Nol'l'nal Normal
hit/disease incr95ed
- 1 gew! delt:tion: Silent carrier. ~-ia Increased Increased Approx. 100% frn:reased
211
210 - 2 ,o,:c>ne deletiolls: Alpha thalassaemia trait. Hypochromic microcytic an;wlt
total body stores. Plasma iron is attached to a plasma protein called transfer· tinued
rin which is the main transport protein for iron. Synthesis of transferrin by the r-:.::.::::_.:::::=::.:..::.:::.::.._________de_fi_.-----,-o-:-la_te_d:-e-::fi:-ci:-en_cy_
liver is inversely proportional to the body's iron stores and is therefon Iron deficiency BJiZ ICiency
anaemia anaemia anaemia
increased in iron deficiency. TIBC (total iron binding capacity) is a functional ~-...,;.:_;___ __:..:.:.:..::.:.:.:..::__ _ _ _ _r_~-..-...-:.-~-.fi:::.sh-:-----:---;-::----
measurement of serum transferrin concentration and is ~pproxirnately 33%: in premature infants, ~--· haemolytic
that is, one-third saturated. Remember that plasma ferritin is an acute phase
presents between 6
and 12 months
tapeworm, intestinal anaemia,
blind loops (812 pregnancy.
:::c

reactant and may be raised even in the absence of body iron stores. because of increased and fat (3) Antifolate
CD
Sometimes questions will ask you to differentiate between iron deficiency needs. Esp. Asian malabsorption). drugs, e.g. 3

-; and beta thalassaemia trait based only on a full blood count. (a} Look at tho families, late weaning phenytoin, anti- ()
> MCV which in the beta thalassaemia trait is usually disproportionately low
fTom breast milk
bo-'-fed bab'a..;.
metabolite cyto-
0
·~ (usually between 50 and 60) compared to the mild anaemia that one sees
,.,....
(3) Malabsorption,
... ~ toxics, e.g.
methotrexate. cc
j '<
en (severe anaemia could be a result of beta thalassaemia major but would usu e.g. acttte.fhydria,
<( ally have been indicated to you in the history). On the contrary however th post gastrectomy,
lower the MCV in iron deficiency usually the more severe the anaemia. ethel W i.----_:coe::.::l=ia<::...:d:.:lse=.:a::.se:.:·_ _ _ _ _ _ _ _ _ _ _ _ _ _ _-:-::--:--
E useful indicators are: (b) that the red cell count is usually reUsed in beta tha Features of anaemia Features of anaemia Features of 812
"'
><
w
lassaemia trait but reduced in iron deficiency; (c) the ROW is very high in iron
deficiency anaemia (>14) but normal in beta thalassaemia trait (this does not
+ koilonyc:hia,
glossitis, brittle hair
+glossitis, jaundice
because of ineffec-
deficiency
anaemia without

-
u
'i:
.~
"0
C1)
co
always occur in clinical practice). In practice Hb electrophoresis and iron
studies (as above) would be performed for confirmation.
Differences between the dietary haematinic anaemias are commonly
referred to in examinations (see Table 8.4).
and pica. tive erythropoiesis.
bleeding tendency
because of reduced
platelet production,
inaeased infections,
reduced white cell
the neurological
features.

c.. production. Neuro-


logical sequelae:
Microcytic Macrocytic anaemia, As for 812
hypochromic hypersegmented deficiency. Serum
Table SA Comparison of haematinic causes of anaemia anaemia, Fe studies neutrophils, and red cell
Iron deficiency 812 deficiency Folate deficiency (see above). Blood leucopenia and folate.
anaemia anaemia anaemia film (see above). thrombocytopenia,
Hb of< 10 g/dl after Howell-Jolly bodies.
Physiology H+ in stomach causes Vitamin 812 Folate from the 6 months of age. Bone marrow
Fe~ -+ Fe 2 • which (hydroxycobalamin) diet is absorbed Bone marrow, hyperplastic.
can then be combines with · unchanged in th4!
erythroid hyperplasia megaloblasts with
absorbed in the intrinsic factor in the duodenum and and reduced nuclear/cytoplasmic
duodenum and stomach which is jejunum. stainable iron. dissociation (nucleus
jejunum. Iron produced by pMietal more primitive cf.
absorption increased cells.. tt is carried to cytoplasm). 812 tests:•
by iron defidency, the terminal ileum
vitamin C and where it is absorbed. Treat underlying Treat underlying Treat underlying
reduced by phytates. cause. Oralli.m. Iron cause. i.m. cause and give
and rarely transfu- hydroxycobalamln folate
Sources Red meat. egg yolk. Animal origin foods. Most foods esp. sion. Continue treat- injections if intrinsic supplements.
green vegetables. e.g. fish, meat. eggs liver and spinach. ment lor 3 months factor (IF} a problem
Requirements and milk. Requirements · after stabili- or malabsorption.
l-2 mglkg/day. Requirements 1-3 100 IJ.g/day. Body sation of Hb to Otherwise oral B12.
IJ.g/day. Stores stores last 3-4 r ...~l ..nii:h stores.
last 3-4 years. months.
of 812 def'tc:iency include peripheral neuropathy, optk atrophy, mental
Causes of (1) Haemorrhage esp. (1) Inadequate Intake, (1) Reduced subacute combiMd degeneratio!' of .t he spinal cord (with a>eltisting
deficlen<y Gl bleeds, e.g. peptic e.g.. vegans. intake rare in of .the d~l columns and pyramidal 17ac_tS).
ulc~ ulcerative colitis. (2) Malabscwption: children.. ~~is a reduced serum 812 level and red cell folate is normal or reduced
Meckel's diverticulum, post gastJectOmy. (2} tncrea5ed entry into the red cell is dependent on vitamin 812. Serum folate Is thus normal
hookworm. pem1aous anaemia. utilisation. e.g.. (since not entering the red cell). to folate deficiency, :serum and red cell folate
(2) Inadequate intake Crohn disease, ileal chronic reduced and serum 8121evels are normal.
Z12 213
I l

+
The Schilling test
An important test of vitamin B12 handling is the Schilling test and you m~ are common in dat~ interpretation questions and in order to answer them
be asked to interpret some results. The test is ca~ out as follows: firstI lhould have a basic unders~ru:'din!? of the following princi~l~ (see Fig·. 8.1).
storage sites are saturated with vitamin 812 followmg an i.m. injection (tl You shoul_d be able to d1Stingu1sh between haemoph1ha ~ and von
Cl) is so that any extra 812 entering the body will be excreted in the urine). rand dlSease (see Table 8..5). To understand the pathophys10logy you
:'2 child then takes oral radiolabelled hydroxycobalamin. Because of the
:l
II (!)_
-cu
rated storage body sites of B12 normally a proportion of ingested ra<llOI• t.
belled 812 will pass into the urine and thus the urine is collected for 2~,.,. ____. .;.___ Ha,M;Oojr;u.;A--=------;;nWI.Ikl;;;;~~;;;;--
.:: (expected amounts ed are between 10 and 30%). A reduction in expected Cc;>ngenital of Deficiency or abnormality
c:
:l
tion indicates r uced absorption of vitamin 812. This test is called
1. The next test (called Schilling 2) involves giving radiolabelled vitamin
Factor VIII resulting in
interference in intrinsic
in Factor VIII:VWF results
in Factor VIII deficiency
C/) this 't ime with intrinsic factor to see if urinary excretio~ increases. If it pathway. and decreased platelet
<( then there is an abnormality with intrinsic factor production. If there is.',W!~-------------------=ad:::h:.::e::.:s:.::io::n.:.:·_ _ _ _ __
increase with added intriflSic factor then there is a problem at the level nf ~••rttan•'~ X-linked re<:essive. Affects The VIII:VWF gene is
E
cu males but random found on chromosome 12.
)(
terminal ileum. lyonisation may result in Inheritance in the majority
w heterozygote female of cases is autosomal

....u
·a:
~
carriers having reduced
Factor VIII levels and· being
symptomatic under extreme exist.
dominant although
autosomal recessive forms

"C Extrinsic pathway Intrinsic pattrway haemostatk demands. High


Cl) (tested by PT time) {tested by 1he P1T time) mutation rate (one-third
cu spontaneous mutation rate).
c..
vu
TISSUB
thromboplastin
1 Vascular 1
endoltlelial
~CXllltad
XII Depends on Factor VIII
levels: (a} < 1% - severe
(50% of cases}.
Clinical features mainly
reflect the platelet
function abnormality (easY
vna XJia Spontaneous haemorrhage bruising, purpura. mucous
into muscle, joint. GIT, soft membrane bleeding,

~j_~ tissue from early life;


(b) 1-So/o -moderate.
Usually bleeding problems
menorrhagia and
epistaxis). Reduced Factor
VIII levels may give rise to
after trauma; (c) > 5% - similar features of

Common pathway
uj_aa mild. Only minor symptoms, haemophilia A but are
e.g. prolonged bleeding
post surgery or bleeding
usually much milder.

T
after severe trauma.
Involve: (a} coagulation Involve: (a} coagulation
tests, (b) factor assays, tests, (b) factor assays,
(c) diagnosis of carriers and (c) ristocetin assay.
DNA

Increased

Ristocetin (a platelet
aggregator) will not
Fig. 8.1 A simplified clotting pathway. NB PT time and PTT times readl adult
2t4 one week and 2-10 months respectively. Table 8 .5 continues overleaf 215
8.6 Comparison of acquired coagulation dison:llers
Disseminated
Vitamin K intravascular
defidency Uwr di~ase coagulation (DIG
Normal Increased

Normal Normal Increased··

Decreased Decreased All dotting


Factors Factors factors decreased.
II, VII, IX, X II, VJI, IX. X (also Increased FOPs.
(normal Factor V) low Factor V)
tunrtic...,..l abnormalities of platelets in liver failure as well as possible associated
leading to thrombocytopenia.
time is sometimes induded in some questions. It Is essentially a measure of active
It is increased in patients receiving heparin, in hypofibrinogenaemia and in the
inhibitors of the formation of the fibrin polymer such as FOP11n DIC. Protamine
thrombin time In all the cases except hypofibrinogenaemia. The reptilase test Is a
for hypofibrin~naemia.

frozen plasma is the result of freezing one unit of blood at -30·c to


approximately 200 ml of fluid with all the dotting factors.
--
1. ·AbOut
-
10%_of..freatea.::paru~nts-<ie:v:Mop:.-EactOr:..VIII.:C antibodies which
lfOt)recioitatecontains Factor Vlli:C, Factor VUI:VWF and fibrinogen.
usually.....t:reated..usmg.Jligh.leV.els~ctO.r'tOLaltemative dotting
·intermediates-(acti'Vated;P~~mbjn-cQIDP.lex)~!Uch·may bypass thr
inhibitor or porcineFjlqor~VIIL,.,
•. ==~~" several slides that you may be expected to recognise that relate to
- 2. ::-Allergie:reactions.~:=:=;:::;~~~:::;::~~~~~~-:::- IIDlogie~ problems:
3. RiSk of as_uirlng1>i~~me=ars'ease, e.,;.gJ!~_i:Ltis B,C.

-
---:-:::::========-----·-·-=.:.....:l poisoning has some characteristic features. You may be shown linear
-~1iti•~ in the metaphysis of bones (similar to growth arrest lines), or split
.:..... ~cqu~d ~~agulation_!l~!e~ - seen on a SXR caused by raised intracranial pressure. In addition
----·•- ""'-'·-= may be shown a slide of an abdominal X-ray in a child with symptoms
signs of lead poisoning. Look for radio-opaque material in the intes-
because of accidental ingestion.
thnlassaemia mtzjor 'is a co~on slide. Compensatory bone marrow
. "'"'-~..... secondary._ to haemolysis cu;l,c;l P.roduces th~ character;istic
,~assaE!miiC ~es~ with frontal bossing and maxillatf prominence.
---•FactorVIII:C - Pol.ogi1cally this can be seen typically in tl}e skull bones with widening of
-~~ -.:.· ~ giving rise to the 'hair on end' appearance (also called 'sun-ray'
STABLE FACTOf1
COMPLEX ltaaan•ce). Instead of appearing bilaterally concave, phalanges may appear
or bilaterally convex. AXR may show hepatosplenomegaly.
Chromosome 12 -Endothelial cell -Factor VIII:VWF / cell diseJzse: There may be a slide of a hand of a child with dactylitis
Fig. 8.2 The formation of stable Factor VIII complex. considerable soft tissue swelling. A CXR may be shown with 217
basal infiltrates, consolidation, areas of collapse and atelectasis in a there is a more fa\·ourable response to androgens and high dose
who is described as being febrile with breathlessness or chest pain. However, treat it like any other aplastic anaemia.
features indicate acute chest syndrome. You may be shown a hip
avascular necrosis of the femoral head related to sickle cell disease.
'-
Q) - RJtdial aplasia: See Chapter 11. ::X:
"C is inherited in an autosomal recessive fashion. 1he syndrome consists of S»
:;::, - Hamrophilia: Look for evidence of arthritis if shown a knee of a child (1)

-
D\b<>Cvto,penia and bilateral radial aplasia (TAR). Radial aplasia is a common
(!) haemophilia. The most obvious feature of artluitis is loss of joint space and you should recognise it immediately. It consists of shortening of the 3

in addition look for osteophytes, subchondral bone sclerosis and cyst and marked deviation of the wrist in a radial direction. Causes include
"'> mation. A psoas muscle bleed can be massive and may be seen on a syndrome, VATER syndrome, Fanconi anaemia and the Holt-Oram
0
0
·~ AXR but should be accurately assessed with CT scan. cc
:;::, '<
fJ)
<t
E There are a number of haematological conditions that have structural of thalassaemia major aims to allow normal growth and develop-
w "'
>< defects associated with them. while at the same time inhibiting extramedullary haemopoiesis, mar-
hvoerot.asJta and preventing bony abnormalities. Be aware, however, of

-0
·c
.!!!
"C
Q)
Diamond-Blackfan syndrome
This is an example of pure red cell aplasia. Ninety per cent present
the age of 1 year, mostly before the age of 6 months. Physical
of overtransfusion and iron overload. Beta thalassaemia major
oft~n require regular transfusions approximately every 2-4 weeks to
ha~moglobin above 10 g/ dl. This has problems of iron ~verload,
antibody formation leading to difficult cross-matching and mcreased
"'
D. ties can be found in about 30%. These include short stature, web neck,
lip and a triphalangeal thumb (instead of the usual diphalangeal
of infection. In cases of increased transfusion requirements or hyper-
splenectomy may be of help. In order to prevent iron overload these
The anaemia is nonriocytic and normochromic and notably has a require iron chelation therapy (using subcutaneous overnight pumps
reticulocyte count. The red cells have certain letal characteristics that which may cause local and systemic allergic reactions as
sist, which include occasional increased MCV, elevated HbF and the as reversible cataract of the lens) with regular measurement of serum fer-
ence of I antigen. Bone marrow reveals a selective absence of red (which should always be below 1000 J,lg/ ml). One should also perforrr.
cursors such as normoblasts. Treatment is with steroids with an assessment of end-organ damage by iron (e.g. liver function tests}.
response of 75% and this response may continue or be of limi~ supplements should be given. Treatment using bone marrow trans-
in which case regular red cell transfusions are required. There lS a (which has a high incidence of graft-versus-host disease) and gene
bility of bone marrow transplant in some. A similar condition called using modified retrovirus vectors to introduce complete globin genes
sient erythroblastopenia of infancy (TEC) must be distinguished front bone marrow are in the stage of clinical trials.
above. It is self-limiting and presents slightly later. There are no fetal L
acteristics of the red cells. The children are phenotypically normal. lt
be preceded by a viral illness such as human erythrovirus (parvov
infection. haematological condition requiring regular transfusions runs the risk of
. Features of iron overload syndrome (haemosiderosis) are dam-
Fanconi anaemia to the .liv.er -~JeadiAg· to hepatomegaly, cirrhosis and possible hepatoma
hepatic failure), pancreas (leading to diabetes mellitus), heart (leading to
This is a form of aplastic anaemia that presents at around 5 years CJI ias and heart failure), skin pigmentation, delayed puberty, and
Inheritance is autosomal recessive with a M:F ratio of 2:1. These childn· gastrointestinal infection (Yersinia utilises iron for growth) which can
be recognised by shortness, microcephaly, horseshoe kidney, absent/ with abdomil1al pain, sometimes with severe diarrhoea, and is treat-
mal thumbs, absent radii (radial aplasia) and sometimes ciprofloxacin.
tion. Cytogenetic problems are common such as chromosome
There is an increased risk of AML. Reticulocyte count is low and
cytopenia may present before full pancytopenia. HbF is_i~creased. It
diagnosed by performing a white cell chromosome frag1hty test and cell disease is a common question. The molecular defect is substituti,H1
218 for characteristic cytogenetic abnormalities. Compared to other I for glutamic acid at position 6 on the beta globin chain. Twenty-five 219
per cent of black Africans are carriers of the gene. Remember other va Aseptic necrosis of the femora I head;
that are inherited in a co-dominant way such as beta thalassaemia, sickle ce As with any chronic problem in children it may lead to growfh problems
beta thalassaemia with a variable presentation an~ickle cell-HbC and delayed puberty;
which has an increased incidence of thrombosis as one of its features.
Acute chest svndrome: fever, increasing dyspnoea, tachycardia and chest
The pathology occurs when the HbS molecules are deoxygenated or becoll)l
pain indicate the possibility. 'The CXR may show increased bilateral shad-
acidotic. The molecules polymerise. This causes the red cell to become
shaped which results in: (a) reduced life span of the red cell leading owing, with collapse/consolidation. There may be only limited sickling
signs -. life threatening;
-> haemolysis; and (b) impaired ci.rt:ulation through small vessels leading to vascv
lar occlusion. Known precipitating factors include: hypoxia, acidosis, deh1 Aplastic crisis whirJl is most commonly caused by human ~g-throvirus
"'
·~
dration, cold and infection: Because of the presence of HbF (which has anU (parvovirus) type Bl9 (like hereditary spherocytosis) and can last up to
j
sickling effects) the condition does not usually present before 6 months 2-3 Wet'ks;
U) age.
Heterozygotes are usually asymptomatic except when exposed to Congestive cardiac failure;
<(
(e.g. under anaesthesia or when flying) . Haematuria and concentrating Blindness caused by retinal infarction and detachment.
E lems may occur.
"'
><
w
You may be presented in a questioR with any of the large spectrum of
sentations.
Investigations: See blood film (above) and Hb electrophoresis (abo:ve); sick-
ling test identifies patients with about 20% HbS and does not therefore
(J distinguish between carriers and those with the disease.
a. Chronic haemolytic anaemia with varying degrees of anaemia
between 5 ·and 10 g/ dl), unconjugated jaundice and - like all
haemoly~c disorders- there is expansion of the bone marrow cavity 1. Acute treatment of painful crisis involves fluids, analgesics, oxygen
ing to sickle facies with maxillary hyperplasia; and antibiotics.
b. Hand and foot syndrome: seen primarily in toddlers with recurrent 2. Blood transfusions (red cells if anaemic or whole blood if sequestration)
and swelling often with fever; are. limited to selected cases to reduc:e problems of iron overload and
c. Bone pain; cross-matching problems. .

d. Chest pain, often pleuritic in natti~; 3. Exchange transfusion is used in two particular cases where there has
been an acute chest syndrome or cerebrovascular ~risis. Following
e. Priapism; these crises it is important that these children have regular transfu-
f. Renal papillary n ecrosis often with haematuria which may lead to le» sions to prevent their recurrence. In any life-threatening complication
renal concentrating ability (leading to polyuria and enuresis) and try to reduce HbS to less than about 30%. Problems associated with
te rm re~al failure; exchange transfusion are: hyperkalaemia, hypocalcaemia (because of
chelation with citrate), hypothermia, circulatory volume imbalance
g . Abdominal pain may be the result of infarction of organs such M (leading to possible heart failure and arrhythmias) and acidosis (from
spleen or liver (and may present as an acute abdomen) but also may
stored blood). There may be reduced oxygen delivering capacity of the
sign of the presence of pigment gallstones; stored blood because of reduced levels of 2,3 DPG (which usually shifts
h. Infection which is the leading cause of mortality is often caused by en• the oxygen dissociation curve to the right).
sulated organisms such as pneumococcus;
4. Chronic treatment involves folate administration, penicillin prophylax-
i. Osteomyelitis - often with unusual organisms..especially SolmonLlla; is, Pneumovax vaccine after the age of 2 years.
j. Chronic leg ulcers are a common problem and take a long time to hl·~l 5. Parental education: Keep the child wen hydrated in the summer, devel-
op the ability to recognise the different types of crises, and so on.
k. Cerebrovascular accident following damage to the cerebral vessels
ing to hemiplegia or cranial nerve palsies; 6.Genetic~
L Pulmonary hypertension; 7. Possible role for bone marrow transplanL
m . Splenic sequestration: there is a rapid life-threatening reduction in \ Sudden onset of anaemia in sickle cell disease may be the result of: (1)
lating blood volume secondary to red cell pooling in the spleen with II splenic sequestration; (2) hypezhaemoJysis secondary to drugs or infec-
idly enl,arged spleen; tion; (3) aplastic crisis. 221
-1-hourly observations and meticulous attention to oral hygiene
Th~re are a number of crises in sickle cell disease: (a) haemolytic crisis; (b) anti.fungals foe Cmtdida prophylaxis. Treat infections vigorously.
splenic ~uestration; (c) acute chest syndrome; (d) aplastic crisis; (e) vaso- I'Ospittal will ha'-e protocols for dealing with a neutropenic fever
occlusi\'e crisis (painful). '-._ antibictic treatment combinations. Resistant infections might be
It is important to know that splenomegaly is often felt in the toddler in ot fungal infections.
sickle cell disease but because of autosplenectomy (arising from repeated %

infarction episodes) the spleen is not usually felt after the age of about -l-5 CD
years (but functionally asplenic from the ag~ of about 1 year). lbe presence o(
Howell-Jolly bod if'S may give a clue to the degree of sple:J\ir function (see ear•
tier). NB This autosplenectomy may occur later in the sickle cell varianU
:viral diseases. bacterial diseases such as typhoid, paratyphoid, TB
in overwhelming bacterial sepsis due to any agent. Remember
(such as HbSC and Hb5-thalass.Jemia) so they must be considered in an oldet 1•1\ab!S have • small ft!Sei'Ve of neutrophils in the bone marrow and once
child with a palpable spleen. have been released neutropenia occurs.
-
3

0
0
ca
'<

. .lcu£11r dysgeMSis: AR inheritance. Abnormality in the production of


White cell counts IBIIOiid precursors. Red cell and platelet production is normal (SCID with
You may be gi\·en questions with differential white cell counts. Don't forg I
the simple rules: l•lfJI,;rn syndro~ (infantile genetic agranulocytosis): AR inheritance.
1 · in the maturation of neutrophil precursors. Associated with a
1. Lymphocytosis is commonly due to viral illnesses such as meas and eosinofhilia. Treatment with granulocyte colony stimu-
mumps. rubella, EBV. TB causes lymphocytosis. Acute lymphoblastic
leukaemia. Don't forget the association of whooping cough with a lyfll improws survivaL
phocytosis. nndropmis; Inherited AR. AD ex spontaneous. There is a 'cycling'
2. Monocytosis is found in infections such as tuberculosis and brucellosis neutrophil count that cx:curs every l4-28 days with an average of 21
well as in chronic inflammatory states such as juvenile chronic arthrlll It a~ aD cell lines but cycling in producti~ will affect neutrophils
a hall life ol ~roximately 6 h) more than red cells (half life 120
OCA). and platelets {7-10 ~ys). Cycle time is usually constant within an
3. Eosinophilia is found in type 1 hypersensitivity reactions includingasthn~~t ••IIVidt.aaL SymplomS tend to improve with age. Diagnose with regular
eczema and hay fever as well as in parasitic infections such as hookworil full blood counts with differentials.
also seen in pulmonary eosinophilia. There is often an increased eosinoplll
••~~~~nu- benigu nnd:mpmia of dr.ildhood: Moderate reduction in neutrophil
count in premature infants.
which remains usually unchanged throughout childhood. There is
4. Basophilia: Chronic mye loid leukaemfl (in adults), ulcerative colitis risk of infection in proportion to degree of neutropenia.
hypothyroidism. syndrome: Inherited as AR condition. (a) Pancreatic
5. Neutrophilia: (a) infection especially bacterial including septicaen11 resulting in malabsorption with subsequent failure to
abscess formation; (b) trauma- post surgery, bums, fractures; (c) druY, short stature (second most common cause of pancreatic
steroids, adrenaline; (d) haemorrhage; (e) post transfusion; (f) s tress: after cystic fibrosis). (b) Deficiency in all myeloid lines
example, post seizure. neutropenia. may also have lower Hb and platelet count.
gingil:itis which may cause premature loss of teeth and cause
of adjacent ..dveolar bone. (d) Hepatom~galy with mild hepat-
Neutropenia (e) Renal tubular dysfunction - rare. (.f) Metaphyseal
mcreased susceptipjli.ty to infection is related to the degree.of neutroptttl
The clinical consequences of ne~openia are of increased risk of inf ·c IUnow infillmtion: leukaemia.. solid tumour invasion, glycogen stor-
from the outside world as well as from sites of the body where there is l\ hi
llila~~SeS. asteopetrosis.
concentration of normal basal bacterial flora which in conditions of
tropenia become in..-asive and pathogenic. Thus oral ~ections/ukenl 4Lficimcy ~as vitamin Bl2 oc folate deficiency results in inef-
gingivitis are common, as are pneumonia at;td perianal infections.. . neutrophil production as well as.otber cell lines.
septicaemia is an additional problem. Treatment depends ~n seventy
For example chemothenpy agents but also carbimazole and chlor-
involves treating any underlying cause. Barrier nursing in a side room,
223
222 ular examination of possible sites of infection (e.g. mouth, perineum
Treatment: Half of all these children will resolve spontaneously by 2 months
Causes of neutropenia increased, t!estruction
(2): of age and 80-90% by 6 months. In view of this, treatment is controversial
- Isoimmune neonatal neutropenia is ~imilar to Rhesus isoimmunisation and is reserved for p latelet counts < 30 and severe bleeding and consists of:
theory. Antineutrophil lgG antibodies ~ bsequently cause (1) M C (which blocks Fe receptors in the spleen) improves platelet count
in infants. within a day for several weeks, although it appears to have no effect on out-
come; (2) corticosteroids increase platelet counts and are given for a couple
- Drugs: In addition to affecting bone marrow, immune mediated
of weeks but ye t again there is no effect ort overall ou tcome; (3) splenecto-
nisms may also initiate immune destruction of neutrophils.
my. Because of the risk of overwhelming infection in this nge group! this is
-Autoimmune net•trOP,tnia associate9 with variqus conditions such as JC reserved only for life-t:hi:eatening bleeding or failure of response to-5teroids
and SLE or may OE:<Ur in isolation. . particularly in the chronic · ITP group (20% complete response to
-Hypersplenism. steroids, 20o/o not steroid responsive, 60o/o partial response). There is a 90"/u
response rate to splenectomy but some (approximately 30%) may subse-
Useful investigations in neutropenia are' FBC (serial if suspect cyclical quently relapse in which case (4) immunosuppressive agents can be used;
tropenia), blood film, antineutrophil antibodies, bone marrow (5) platelet transfusions may be used in severe bleeding (such as intracra-
(to look for myeloid precursors and to exclude infiltrative causes). nial bleeds) but will be rapidly cleared from the blood by the antibodies.
Qualitative disorders of neutrophil function are discussed in Chapter 9
uses of neonatal thrombocytopenia
Thrombocytopenia MllttTJUll idiopathic thrombocytopenic purpura: Look at the mother's platelet
A common question relates to the child with thrombocytopenia. You s.tw!elllj count. This is not always reliable and the count may be normal if she has
look up a list of all the p ossible causes o f thrombocytopenia under the had a splenectomy. Look for antibodies. May last 1-3 months.
ings of: (1} reduced production; (2) increased destruction. Discu$ed hel1 lsoimmune neonatal thrombocytopeniJt Theory as for Rhesus haemolytic dis-
the commoner examination topics. ease but :with anti-PLAl antibodies passing to the fetus of an anti-PLAl
negative mother. Normal.matemal platelet count. look for antibodies. Can
Idiopathic thrombocytopenic purpura (lTP) last 1-3 months. ·
Affects children typically between the ages of 1 and 5 years old. M :F ratllt
Acute onset of purpura/petechiae, ~osebleeds or bruising in an
well child (more rarely haematuria or mucosal bleeding). Evidence of
Birth asphyxia caused by depression of bone m._·rrow.
ing ~ only seen in platelet counts < 20 x 10~ /1. Most follow a recent vir•l
ness. Most importantly in the history and examination you should
for the lack of recent weight loss, the absence of lymphadenopath~
abnormalities such as WlSkott-Aldrich syndrome, TAR syn-
he patosplenomegaly (splenomegaly may indicate leukaemia or
and no indicators of other illness. ln other wo rds the child with ITP loob
ically well and is in fact well. Haemangioma causing platelet destruction (Kassalbach-Merritt syndrome
You may be given some investiga tion results as follows: Low -see Chapter 12).
count, Hb normal, wee normal. Anti platelet antibodies may occru;tol,lll~
MattTJUll drugs, e .g. some antibiotics.
found but are not necessary for the diagnosis. Bleeding time is prolc>nAIIII
Bone marrow examination is ~rformed only if there is an atypical n mlours (rarely) ca~ by leukaemia, neuroblastoma.
tation, tO exclude leukaemia or aplastic anaemia or if it is intended
steroids which may mask an underlying leukaemia by destroying
cells, or precipitate a possible tumour lysis syndrome in an inadequattly lllallttllt h re platelet defects
~red child. Bone marrow will show no~l or increased platelet .IIU1:n~~r of qualitative platelet defects p~nt in the paediatric patient and
(megakaryocytes) indicating peripheral destruction. recognition may be tested in an examination question (see Table 8.7).
The most severe complication is intracranial haemorrhage which CX! qualitative defects include WJSCOtt-Aldrich syndrome (small platelets
less than 1%. Chronic ITP- lasting more than 6 months- occurs.in 5-o- thrombocytopeni"a), May-Hegglin anomaly (associated with thrombocy-
cases. It is commoner in young female adults usually over 10 yeara with large platelets and abnormal white cells), Chediak-Higashi
(beware transplacental transfer of antibodies in a mother with chl"()ll 111t11-orr•P (abnormal platelet function). Uraemia and chronic liver disease may
causing neonatal thrombocytopenia). Antiplatelet antibodies are cause platelet dysfunction. 225
224 about 70% of cases. It has a variable course.
(trephine biopsy or aspiration from two or more sites) will be hypocellular
Tilbk! 8.7 A comparison of Glanzmann thrombasthenia and Bemard-Sour.er (and in severe cases produce a dry tap).
syndrome Treatment is supportive with transfused red cells and platelets, prevention
Gl•nzmann lnd treatment of infection (see also management of neutropenia above).
t/lrombastfleni•
Androgens, antilymphocyte globulin and high dose steroids are also used.
Autosomal re<essive Autosomal re<essive Ideally treatment co~ists of an HLA matched bone marrow tr~nsplant. You
Appearance and Normal platelet count Mild thrombocytopenia lhould be familiar with the dini~~l features of graft-versUS>-h~t d~ase (a
number of platelets and morphology and vety large platelets possil:>le grey case scenario) which presents with skin rash, diarrhoea and
IMeding time Increased Increased Jlundice as the mai}l features and is treated with cidosporin. It may also be
Platelet surt.ce Deficiency in GPIIb and Defjpency in GPib and lien in some conditions where the patient receives non-irradiated blood.
glycoprotei~ (GP) GPIIIa GPV
involved in platelet
function l.rmphadenopathy
Platelet aggregation No platelet aggregation Platelet ~egation Whenever you come across lymphadenopathy it is imperative m the clinical
studies with any of the platelet normal with ADP and tpmination that you should also look for e\'idence of sepsis in the region
agoni~ts (AOP, collagen collagen but abnormal
and ristocetin). with ristocetin. *-ined by the lymph nodes, hepatosplenomegaly, lymphadenopathy else-
Where and evidence of BCG vaccination (scar on left arm). Other than haema-
Treatment Treat bleeding episodes Treat bleeding episodes
wittl platelet transfusions. with platelet transfusions. IPJogical malignancy and lymphoma you should also think of other causes
Beware isoantibody Beware isoantibody ~uding the following infectious causes: pyogenic lymphadenitis (e.g .
formation. formati91'1· flt,plr., Strep.}, tuberculosis, atypical mycobacteria (most often cervical, post
M&rlcular or submandibular), typhoid fever, EBV, CMV, toxoplasmosis, cat
ICratch disease (following a cat scratch a papule or pustule typically develops
A»llowed approximately 2 weeks later by regional lymphadenopathy which is
Pattern of anaemia with abdominal pain tha~cte_~tically unilateral with fever and malaise}, sarcoidosis, histoplas--
1111515, lymphogranuloma iriguinale (inguinal lymph nodes} and YersiniD.
The pattern of a child who presents with anaemia and abdominal pain could
be caused by the following: sickle cell disease, lead poisoning, glucose
6-phosphate deficiency, bleeding site in GI, vasculitis (e.g. Henoch-Schonleln Dlher main causes of pancytopenia
purpura) and chronic disease with GI involvement (e.g. Crohn disease).
HYf'"Splenism: This is an enlarged spleen associated with the reduction of
Aplastic anaemia one or more of the blood cellular components resulting in decreases in red
cells, white cells and platelets. Causes include: (a) Inflammatory causes
This will usually present in the form of a pancytopenia. Causes are:
41uch as SLE. (b) Infections, for example infectious mononucleosis. (c)
- Dmgs: Dose dependent such as chemotherapy agents or idiosyncratic Me~~ ·.-•:-: diseases, e.g. Gaucher. (d) Congestive causes: that is, any condi-
such as chloramphenicol. tion causing pv. \:.:~ ~~'!"ertension such as cirrhosis. (e) Lymphoproliferative
- Chemicals: Benzene ring solvents, carbon tetrachloride. dhiOrders, e.g. leukaemiasi t:p-1;;::-"'"mas (see Chapter 6).
- Viruses: Transient in infectious mononucleosis, hepatitis A. Human In hypersplenism (d. aplastic anaemlil) ti::: :eticulocyte count will be nor-
erythrovirus (parvovirus) type B19 can produce a transient aplastic mal or increased and the bone marrow if examined w.;;~~--! ~ hvpercellular.
anaemia in sickle cell disease and hereditary spherocytosis. Splenectomy usually reverses the changes.
- frradwtion.
- lnlzerited causes: Fanconi anaemia, Shwachman-Diamond syndrome. lnjiltratio11 of tire ~IJe marrow: Leukaemia, neuroblastoma.
- JJiopotlric. hncyto~niD may also be seen in haemolytic uraemic syndrome and in dis-
Clinically there will be features reflecting a reduction in the red cell, white c~ll intravascular coagulation.
and platelet lines: that is, anaemia, increased· risk of infection and bleedlna
Remember that an important clinical sign ~o dete~e is the presenoo I
absence of splenomegaly since this will help differentiate ~m leukaemiA
Investigations are as expected from above: low platelets, low white ''' questions gi\'e you a history of a child suffering from acute arthritis and
counts and low Hb with however a raised MCV. Reticulocyte count (II count which shows the child to be anaemic. The causes of this com-
. _ .lirln include the following:
226 indicator of bone marrow function) is low. Bone marrow examino~t!l 227
.... Sickle ctll ciise?.se in an appropriate racial settin~
-- Acufe let.tk.rlertti4'
--l\lec:oblast..;ma
- · Tnl! ..-:t.ronic dis-e.::~ th<Ot 1\.t\'e a rcormocytic nonr-ochrorruc anaemia as
~rt of 1}4-~t p;·.e-.::~n•·aacn st.,cn as JCA, SLE., 'IB :-.rthritis and neoplastic
poor renal perfusion and •-enal ve.in thrombosis.,.
•••hn•lir·
- ..... ,•• ,J~... ,·nr· thrombocytopenia
.

IIM!tirn,t.u··u: stiff non-<ampliant iungs, pulmoMt"J hy~rtension.


.
hypoglycaemia. hypocaka~ ;ma ,,nd hyperl>h!rubmat"\'X\:a
I+
I
irrvoJv?~t ci e1 joint:

..
"r~ l!~!n!1Sm
A PCV of 6..c;.....70% and asymptomatic 'an ba tre-'tted with increasing
Babies with a PCV > ?\r.. or symptor.-tatic with a lc.wcY PCV may
a dilutional exchange trar.s{uslo n . I
lllt totlowing arc asrociatl.'d wHh hyposplenism: sickle cell disease. ulcera- ltl~lt<aeJ:;\!<1 m clrler children
tive colitis, Fanconi .maerrJ~. tmpi<:<!l spru~ and coeliac disease. have primary ane secondary causes. Primary polycyi:l"lclel\\id is
in adults. S::!COndary \:auses of polycy1t>aemi:l are: (a) chronic
i
ij,,
En'l..'"l!Ni biicdKl.:mjstt'}• e.g. cyanotic congenital heart di~aS(.', high a ltitude; Cb) ~pk ery-
•!ll~tin production from tumours such as C\:!rehe\lar hclemangJob!c~.stoma.
A com mon question' that is often alluded to in Vdrious f~>rms is the errors that •nv•::trc>nE~orlro~15 and renal cysts; (c) haemocon~entration !spurious) as·'
one rnight expect in biochemistry when:
dehvdration (many causes). ·
a. Blood is kept for a long ~riod before being sent to the laboratorv: raised · include arterial blood gas Pa02 ~timation and ery-
potassium , phosphate, AST. Tnis is caused by the leaking of these.intracel- •&letin levels as well as any additional tests to exclude a seconaary
luiar-rich component.<> through the red cell mernbrane into the extracellu- Erythropoietin leyetc; are elevated in secondary and low in primary
lar compartment.
b . Blood is haemolysed, for example because of a difficult venesection: raised
potassium, phosphate, ASf. llllaci~m,OClllobie~«!:m.ia

c. There is prolonged venous stasis during venesection: high ·p lasma dlldum, common question relates to the baby or child who has methaemo-
increased total and individual protein fractions, increased T4 and increased llis...-.~;,.,
Clues to the diagnosis m ay be giVen in the hiStory such as the
potassium and phosphate. This is the :result of increased hydrostatic pres· appeared cyanosed but had a comp!e tE>ly ·normal cardio,·asculaJ:
sure causing fluid and electrol)'tes to ~eave .the vascular compartment, examination with a normal CXR end echocardiogram.
!eaving the larger p~teins and p mtein-bound ions in the '\'e5Sel causing blood gas is usually nonnal. Blood sampling from such a baby
their higher concentration in the blood sample. b lood with a bro\-\--Tiish colour; unlike in the normal i.ndh•idual fuis
__ ,,t tum red on e"posure to air (filter paper t.:st). A persistent brown
d. Taking blood fmm an arm with an inf•Jsion running into it: a ll concentra implies a metHb level of more than 10%. Cyanosis develops if b"'l.e
tion!> will be more dilute <ind the glucose, sodium cmd potassium concen concentration is > 2 g/ dl. Babies may be lethargi~. tachycarrlic and if
tration.:; wiU a pproach the concentration.of the hLfused fluid .
comatosed.
It occurs when the iron is in the oxidised ferric (fe3") form. Jhis
Polycythae mia
of haemoglobin cannot bind oxygen and is thus functionally useless.
Some questions will ask you to identify polycythaemia (either in slides, grey are particularly s uS<"eplible to deve lop m~that!rnogJobin.aemia
cases or data interpretation q uestions) s<> you s hould have a scheme. -""''I'" t.'leir antioxidative abilities are not yet fully de'l:eloped. ·
ritnl: Caused by: (a} an abnormality ot the enzy mes that keep haemo-
Neonatal polycytha.::miil
i..i'\ the reduced F~- state (NADPH methaemogJobin reductase
Oefinec.l as a haemat<;Krit '> .65% and can be caused by: fUGR babies, large for
ex.ists in a heterozygous or homozygous fotm); or (b) the result of an
dates babies, poot-mah.ue babies {last three cases due to intrauterine hypoxia),
1 haemoglobin molecule that keeps haernoglcibin in the ferric form
infant-s of diabetic mothers, babies '!!'.lith Do"Wn syndwme, blood transfusion
haem oglobinopathy - dictgnosed on Hb electrophoresis).
(twin-twin, delay-ed clamping of the cord} and congenital adrenal hyperplasit1
TI\ere i.s an" ex}-">Onential increase in blood v:.s~itv abOVe 65% which : This occurs when the child is expo<..;.ed to ce;tain nxidani'S. Agents
results in the hype•:viscc.sity syn~rom.e. • nitrites (sorru~times found in high con<:en~tion in water. hom
nitrates, anilin~ Qyes, drugs s uch as sulphl>namides, d~t;.sone and
Skia: pletllor..:, t:y<mosis
2~ - N ·urologictJI: jitrery, intracraniai t:"rombosis, s~izures wtm;aa1L.Ilrle and babies treated with nitric o~id~. 229
Carbon monoxide poisoning
An important problem that you shoulc13<now about. Its sources include mn•~roblciStc:>m~.a (results in raccoon eyes)
vehicle - e~austs, natural gas combustion devices fespecially if there is •IDClornyos;ln:onw
enclosed an~a with poor ventilation), burning charcoal. kerosene or natural
(e.g. in heating). Carbon monoxide poisoning is thus commoner in the injury ..
months. Carbon monoxide binds rapidly with haemoglobin with an affiniltt.D lY may be confused with a periorbital cellubtis.
about 250 times that of oxygen to produce carboxyhaemoglobin (COHb).
results in blood having a low oxygen content and a shift of the oxygen
ation curve to the left. Acute symptoms are a result of hypoxia
myocardial and neurological) and include headaches, dizziness, nausea (~-po 1rta 1n1 topic, as it is the cause of about 30% of all childhood cancers. It
misdiagnosed as flu) . Other people in the environment of the patient may bv the proliferation of a single bone marrow stem cell that has
similar symptoms. In infants vomiting may occur. The classic cherry red ~alignant transfonnatio~. . .
very rare, occurring in only abo ut 2% of cases. Cyanosis does not occur and signs arise as a r~ult of bone marrow infil~abon With
skin has a pink colot.:.. ::;ynr:ope and seizures may occur and this is cells resulting in the effects of pancytopeni~ ~iltrat_10~ of ':ath;:
coma and death. Even after recovery trom the atui-... J-lr3.::~ sequelae may of the body and an increase in the basal.metabo · m sustauung a r
These include memory disturbance, movement disorders (secondary to mass. ka . f
ganglia involvement) and ataxia. Measure the COHb levels (not a good lymphoblastic leukaemia (ALL) ·is the commonest 1e~ emta ~
late with the patienl's di.cucal condition or prognosis, which is related to peaking at 3-4 years of age. Acute myeloid leukaerrua (AML) 15
toxicity). In non-smoking individL'"lls a level of COHb more than 5% acute leukaemia in adulthood but both can occur at any
CO poisoning if the patient has not bet:;. g:·n:._n 100% oxygen for more than leukaemias are very rare in children (85% ALL, 14% AML,
Blood gas and oxygen saturation are not useh.: i-:-. rlc;lo-ti i.;_-.: L"\r. the panf1•t:MI
level of hypoxia (underestimated). BlOod gas is useful to llctermine the acute leukaemia there is an increased amount of blast cells in the
of metabolic acidosis which resolves.on correctirlg the hypoxia. Trec.t with blood whereas in chronic leukaemia there is an increased amount
oxygen with a tight fitting mask (reduces half life of carbon monoxide fron1 !-looking leucocytes.
to about 1 h). Treat hypotension with fluids and seizures with anltlCCinVl
Consider hyperbaric oxygen treatment if severe symptoms or COHb > 40C)I•Inltation
the sake of the exam be familiar with the modes of presentation: a short
Gum hypertrophy of being unwell with symptoms related to anaemia (~allor: tiredness),
(bleeding) and leucopenia (increased infections).. Bo~e
A possible slide question is a child with gum hypertrophy and you (common in children with leukaemia because of blast accumulation Ill
have a list of possible causes: M4/MS acute mveloid leukaemia and ,..,.. ......, . recent weight loss, lymphadenopathy and ~ep~tosplenomegaly
such as phenytoin and ddosporin. • common in ALL than AML), anorexia, headache, dlZzmess_and blurred
d vomiting are accompaniments to CNS mvolvement
nausea an ?S"Ic0 f ti. ts)
Haemorrhagic disease of the newborn is mmmoner in ALL than AML, occurring in up to o pa en ·
hvperviscosity syndrome can occur with bla~t co~ts > 1?0 x 10"~~1
The occurrence of gastrointestinal bleeding in a seemingly weD looking ca"use headache, confusion and focal neurologtcal s1gns. ThiS ~o.mph­
baby between the second and slXth days of life should raise the suspicll•, may be partly protected by the pancytopenia but may be prec1p1tated
haemorrhagic disease of the newborn. It is caused by vitamin K deficiency
a transfusion.
earlier). Babies most at risk are breast-fed babies, asphyxiated babies,
.md small for dates babies and maternal anticonvulsant therapy. Treat
bleeds with fresh frozen plasma and prevent with oraJ/i.m. vitamin K. (
cell count can be nonnal, increased or decreased with a norrnochrom_ic
causes of haematemesis or PR blood in a well looking baby include
...fte,,tic anaemia with the presence of large numbers of lymphoblasts (m
230 maternal blood at deli,·ery or from cracked nipples during breast feeding ) or m yeloblasts (in AML). Platelet count is low. In AML one may see 231
I

Auer rods in the leukaemic cells which are cytoplasmic inclusion bodl CNS prophylaxis: Cranial irradiation and intrathecal methotrexate usually
{pathognomonic of AML). The bone marrow is hypercellular packed wl post remission. Regular assessment for relapse is essential. lhis includes
blast cells and it is essential to sample the CSF looking for blast cells indiCI looking for bont? marrow relapse (poor prognosis, consider BM1), CNS
tive of CNS involvement. relapse and in boys testicular relapse.
Q)
:2 Prognostic factors in acute leukaemia Complications of treatment :I:
:s Prognosis worse if: (a) male; (b) WCC > 30 at presentation; (c) age less tlw I»
CD
(!) Chemotherapy-induced bone marrow suppression pancytopenia with
1 year or older than 10 years at presentation; (d) morphology - U, L3 wm
risks of infection and bleeding.
3
cu prognosis than Ll; (d) abnortnal chromoseQ1es present with translocatio~ I»
.~ (eY cytogenetics- haploidy a worse pcognosis'than·j>olypJOidy; (f) B cell wot Tumour lysis syndrome. lhis is commonest in those with the highest white
[
i! prognosis than T cell; (g) CNS involvement at presentation; (h) bulky elise• 0
cc
:s cell counts and bulky tumc;>urs. It occurs following the rapid destruction of
fJ) with hepatosplenomegaly and lymphadenopathy; (i) failure to induce a ren1~ the leukaemic cells. This destruction is accompanied by release into the cir· '<
<( sion within 14 days; (j) black children generally have a worse prognosis. culation of large amounts of potassium, uric acid and phosphate. In a data
question look out for the biochemical features of: hyperkalaemia, hyper-
E
cu
Classification of ALL
phosphataemia, hyperuricaemia and hypocalcaemia occurring usually
>< The classification of ALL can be remembered as MICE.
w within 24 h of starting chemotherapy. There is a potential for renal obstruc-
• Morphology: Refers to the morphology of the lymphoblasts and called l tion secondary to uric acid and calcium phosphate precipitation in the kid-

-
CJ
·s:: 2, 3 (85% of ALL are Ll). neys (more likely in aci~ conditions). Prevent with hyperhydration and
.~ • Immunological markers: Describes from which type of progenitor cell II alkalinis;;ttion (sodium bicarbonate) of the patient before commencing
'C
Q)
malignancy is derived: B cell, T cell (older boys), non-B, non-TALL, rt chemotherapy and administration of allopurinol until the wee has sta-
cu type; 80% a.r e from the common non-B, non-T cell type. bilised (various regimens exist, the aims of which are to reach an ideal uri-
a. • Cytogenetics: Thi~ describes the number of chromosomes in the leukaetl nary specific gravity, urinary volume and urinary pH). Closely monitor
cells which is usually above the normal 46 component. The greater I U&Es, calcium, phosphate, urine output, pH and specific gravity regularly
number the better the prognosis. du$.g treatment.
• Enzyme studies: Terminal transferase present in 95% of ALL.
3. Second malignancy.
There is a morphological classification for AML (Ml-M7) that you sho
4. Cranial irradiation can damage the pituitary gland and hypothalamus
know exists.
resulting in growth failure and other consequences of pituitary dysfunc-
Treatment for ALL tion. Spinal irradiation may cause stunting of spinal growth.
This is only a broad outline since protocols are continually evolving n
changing.
Supportive measures include correction of anaemia and thrombocytopt
with transfusions and treatment of dehydration as well as the prevention ~
treatment of infections (~o-trimoxazole for PCP prophylaxis).
-Induction of remission: Chemotherapy for weeks 1-4. A combination of 1,
drugs is used such as prednisolone, doxorubicin, asparaginase and w
cristine. The combination will vary according to the prognostic types of
leukaemia. The aim is to eliminate blast cells from the bone marrow. A
remission rate with return of normal blood counts with normal haemopol
and e~ation of the leukaemic clone.
- lntensiftcation/consolidation: In order to remove any remaining malign
blast cells further combinations are given, often using some of the
drugs used in induction.
- Maintennnce: lhis involves weekly methotrexate and daily 6-mercaptop11
(both orally as an outpatient), in addition to monthly pulses of vincriNI
232 This treatment is given for about 2 years.
233
mmunology 9
is an important topic since several questions ask you to recog-
immuriodeficiency diseases and patterns, and discuss their
and management. This chapter attempts to cO\·er the main
}ll• •noaelrta.enctes emphasising in particular the theory and points that are
referred to in the examination.

• tlmlllllrog.enicif:f!:. The capacity to drive an immune response.

-•mr1r·ve11icity: This is the property of being recognised by .an antibody.


llll'illDpe (determirumtJ: This is the small~t/minimal part of a molecule with
an antibody or cell can interact
• •J7lf!lll:. This is too small to be immunogenic but has the potential to be epi-
if it is coupled to a carrier molaule.
This describes the abili~f to detect very small differences
foreign bodies.
. This describes the immunological phenomenon that develops
previous exposure to foreign material. This response is made use of
vaccinations.
response: This occurs oa first exposure to an antigen.
•ract:eriisti1cally there is a delayed response which is of short duration
weak potency. lt consists of an lgM response.
r~ponse: This occurs on sul:sequent exposure tv the antigen. It is
onset, greater potency and longer duration as compared to the
response. It consists of an lgG antibody response.
This is the ability of 'the body to recognise self as self and not
r.rnto>r1nrcr-.
an immunological response a~t itself.
235
Q)
3
·-
"C
3
s:::
-~ ::l
~
0
·~ (Q
::l '<
en
<(

E
C'CS
)(
w speaking severe disorders affecting T cell function also have an effect

-
u
'i:
.~
"C
Q)
C'CS
humoral immunity since antibody production is partially T cell depend-
Abnormalities in T cell function typically cause an increased susceptibility
Viral, fungal, protozoa~ and TB infections. Symptoms are generally more
fflere tha':' with humoral defects. Failure to thrive is coo:uno~er than with
c.. Marnoral diSOrders, and these disorders may often be fatalm childhood.
Abnormalities of antibody-mediated immunity
_./
IgG is the only antibody type that crosses the placenta to the fetus from combined immunodeficiency (SCID)
mother. Thus it is IgG that confers immunity on the fetus during the firsl are a number of questions that relate to SCID so it is important that you
months of life. The full complement of IgG is reached by 3 years of agu. -~o-n:;..., the usual clinical pattern.
transplacental transfer of antibody occurs afrer about 30 weeks' is a failure of differentiation of stem cells into T and B cells. Inherited
only, and therefore a baby born prematurely before this time will not of (a) X-linked (50%); (b) autosomal recessive (50%- SwisS-type). Fifty per cent
receive this conferred immunity. Since there is no IgM transfer across th• AR inherited SC1D type have an adenosine dearninase deficiency.
centa any IgM antibody found in the cord blood or neonatal blood
birth can be assumed to be caused by an intrauterine infection: that
duced by the baby in response to the infection. The full complemen t of
reached by 1 year of age. Infantile sex-linked Common variable Selective lgA
Antenatally acquired IgG in the baby decreases to very low levels by hypogammaglobulin- immunodeficiency immuno-
4 months of age. Infant IgG and lgM increase only slowly from b irth aemia (Bruton disease) (CVJ) deficiency
there is a period between approximately 4 and 6 months when tlie bllllf X-linked inherited Abnonnality in Most common
Low antibody levels (awaiting infant immunoglobulin production) and I• condition w ith males ability of B cells to primary
atively immunodeficient. This time period is referred to as -.ffected only. . produce antibodies. immuno-
Abnormality in 8 Normal circulating deficiency (1 :700).
hypogammaglobulinaemia of infancy.
lymphocyte differen- Sevels of B and T Circulating B cells
lg~ is the major antibody of bodily secretions found in saliva, teart. tiation leading to cells. Reduced are normal.
secretions, breast milk and sweat. The full complement of lgA is absent B cells and antibody levels, Normal Tcell
14 years of age. IgD is present in rnirw,Je concentrations in blood a'l'ul normal T cells. Absent especially tgG and function. Normal
bodily fluids. lgE binds to Fe receptOrs on the surface of mast ctll plasma cells in bone A with normal lgM. concentrations of
marrow, lymph nodes ~addition T cell other circulating
basophils. When the igE molecules are complexed with a specific classes of anti-
and gut. Very low function is
there is a triggering of the release of inflammatory mediators (degranll levels of serum fg. abnormal. bodies. lgA levels
and this is the basis of the type 1 hypersensitivity reaction. usually less than
There will be dues in the history that should point you in the d in., Smgtdl.
a humoral immunodeficiency. The disord ers of antibody-mediated
236 'Dble 9. 1 continues ovrrleaf 237
Gl:;ab~le~9-~1~G~on;;ti~ni.N!C1;;;----------------------1.llunw•:nic skin infections are also typical with cutaneous candidiasis, herpes
------~ln~fa~n:titi~le~s;;;e;x:;.ftit·n;Ak;edd-(::;;;;;;;;:;:;:-:;;::::.:::;:;-::---=--:--:---- ~
varicella infections. These children have no lymphoid tissue and an
hypogammaglobulin· Common Y<~riable ~ lgA r.en t thymus (compare with Bruton disease where there is little lymphoid
) Th
immunodeficiency
aemia (Bruton disease) (CVI) 1·
~ ~ but the thymus is present . us there ·ts no hepatosp1enomegaly or
Clinical features Otuet after a few delideucy p.p hadenopathy in response to infection compared with common variable
Clinical features "--
months. Recurrent appear in later ~omatic 1111111unodeficiency. 3
infections especially childhood even up or mild Most infants have lymphopenia (a possible clue in the question). In acidi-
3
-~ of the lungs and
paranasal sinuses
to the second =msty. Soma llan there will be reduced T cell populations and reduced CD4 helper cells
decade. Chron~e· and patients have an ~ anpa red t o norm al as well as red u ced numbe rs o f B cells·. Abnonna·1 T cell
c
::s
(sinopulmonary). 0
·~ Most common recurrent increased ~tion tests and reduced G, A and M antibodies will also be found. 0
:I pathogens are sinopulmonary
infections occur. In ·•n<idenee of 1ireatment consists ideally o f a bone marrow transp1ant w hich
· provides the cc
t/) '<
Staph. aureus. addition chron~e· sinopulmonary lftly possibility of cure. Aggressive treatment of infections. Prophylaxis with
..
<( Strep pne
·
Haemophilus
umoniae, diarrhoea is
infections,
gastrointestinal
D photericin (against Olndidll) and co-trimoxazole (against Pll~umnrustis).
--:7
E influen.zae. There is common, often infections (such Intravenous immunoglobulin is given intermittently. The child should not
~ relatively little ;econdary .to Giardia as with Giardia), !Kfrive any live vaccinations. AU blood products given must be CMV nega-
w lymphoid tissue in ~mblia (malabsorp- allergies and dve and irradiated. The latter is done to prevent graft-versus-host disea.,.,.

-(.)
t1on and villous """'
·;: comparison to the atrophy possible). autoimmune jGVHD) caused by the introduction of functional lymphoid cells into a child
frequency of diseases ..A..-

.!
.infections. lymphadenopathy (rheumatoid '".., is immunodeficient. Features of GVHD are hepatosplenomegaly, lym-
'C and splenomegaly arthritis, SLE pbadenopathy, skin rash and diarrhoea.
Cl) occur (d. Bruton and pernicious
C'G disease}. Increased anaemia).
Q. autoimmune Mscott-AJdrich syndrome
d~cfers <haemolytic Dtis is inherited in an X-linked fashion and there is a combined B and T cell
a~mia, ITP and defect. This syndrome consists of immunodeficiency, chronic eczema and
.,emicious anaemia) throm~topenia (with very small platelets that are rapidly d~troyed by the
and risk of
1pleen)"as its main featU'res. IgA and E are raised and IgM is low. There is a
malignancles (non-
Hodgkin's lymphoma, poor antibody production response to polysaccharide antigen and thus the
Treatment gastric carcinoma). children are prone to infection with encapsulated organisms such as
Early diagnosis tO Early diagnosis
prevent chronic lung and aggressive Symptoms are Haemopl1ilus influenz.ae and Streptococcus pneumonille usually in the form of
dl~ase. IVIG usually s0 mild tinopulmonary disease. The coexisting T cell abnormality gives rise to an
treatment of as not to require Increased incidence of infections with viruses such as herpes, CMV and
(intravenous immuno- infections as for
globulin). Aggressive Bruton disease. treatment. Pneumocystis jiroveci. There is also an increased risk of lymphoma and auto-
antibiotic treatment Children should
Immune diseases.
of infections. not be given lgA
in any form Treatment involves aggressive treatment of infections. Intravenous
since sensitis- immunoglobulin is sometimes used. Splenectomy can increase platelet counts
ation can occur but a matched bone marrow transplant will reverse most of the abnormalities.
and.may lead to A possible slide question is of a child who is described as having recurrent
anaphylaxis. This
includes order- Infections who has widespread eczema and possibly petechiae (from throm-
ing lgA deficien1 bocytopenia).
blood for
transfusions. Ataxi~ telangiectasia
This is inherited in an autooomal recessive fashion: it is a combined B and T
cell defect. The syndrome consists of cerebellar ataxia starting in the first 5
It presents usually in the first few . years, oculocutaneous tf!langiectasia starting usually after 3 years of age,
there is a failure to thrive R . months of life (usuallv < 3 months) an~ ft!Cllrrent sinopulmonary infection often leading to bronchiectasis, mental
. . . . esp•ratory infectio , '
tunlStic •nfection such as with Pnrum . ~ are. common ~ an oppot retardation with growth failure in later childhood and immunodeficiency that
corinii) or CMV is typical G .... . . ocy~hs JI~CI (formerly Ptrn~mnru</11 ~ ~ell-~ediated and humoral !Jnmunity. There is an increased suscepti•
. . . · as .. omtestinal mfect· --r
238 tc d•arrhoea, chronic Gl candid' . c· . IOns are common with chrol1 bility to malignancy especially to lymphoma, leukaemia and medullobln
lilSJS, lardw and Cruptosporid· . L •
toma. Patients display radiation sensitivity of their DNA with increnM"d
· ;,, . 1um tn•ectiom
------'
chromosomal breakage (which can be observed in cultured leucocytes ami
fibroblasts). Bloom and Fanconi syndromes are other syndromes that demon•
strate chromosomal fragility. Typically one fmds low levels of IgA and E with
the presence of low molecular weight IgM and very low levels of IgC2.
Alphafetoprotein is raised as is CEA. In some cases where IgG2 is low MG
may be used with some success. Aggressive treatment of the lung infectioru
will slow the pulmonary deterioration.

->
cu DiGeorge syndrome
There are a number of abnormalities that result from abnormal developmer11
·~ of the third and fourth pharyngeal pouches during intrauterine life. There 11
:::'1
U) a spec~m of severity of disease. There is thymic hypoplasia (T cells aro
<( reduced to l~s than , 30% of the total circulating lymphocytes - normally •llla.k-·H~sta~~hi S\'lndlroD:te
.. 40-80%) leadmg to mcreased susceptibility of infections. HJpocalcaeml~ ~-~
E
cu results from absent parathyroid glands and usually presents in the first few
.,..:._, _ _..J

)( days or weeks classically as hypocalcaemic tetany. Typical DiGeorge facie,


w

-
include hypertelorism, low-set malformed ears, antimongoloid slant to tht
0
'i: eyes, micrognathia, carp-shaped mouth and cleft palate. Cardiac abnormal!
ties occur commonly and these are usually truncus arteriosus and interrupt
.~
"C
CD
cu
ed aortic arch. B cell and antibody function is intact. Treatment may consist ol
a fetal thymus graft. Blood products should be irradiated. A possible slid .· .... ,
.-.... ...'
.... - · i

c.. question may consist of a child with typical DiGeorge facies and a mid immlitlOima-totas disease (CGD) · 1
sternotomy scar from a cardiac correction. Another slide may be of a CXR film r-cc~nclition is-nu:e with a 75% X-linked inheritance and 25% autosomal
of a neonate who has no thymic shadow ami has a concurrent infection. HeN . .~i·ll~-ilrll1,eri.tari - There appears to be an abnormality in the NADPH oxi-
the possibilities include 5CID and DiGeorge syndrome. in the neutrophil membrane. nus results in a failure of ~e neu-
to_,p['(>dtl~ super-oxide radicals as part of their killing mecharus':' ( th~ _ i' '

Chronic mucocutaneous candidiasis· irii;:lu-de.hli•<b02'el'l peroxide, hydroxyl free radical and supe:oXld~)-
This is aT cell abnormality with a resulting cell-mediated immunity defect 111 ~~~~~aJ~ in the first year of life with particular types of infection- -
·-·
. -.J

Candida. This results in chronic Candida infection of the skin, mucous mem• I o~ms described as catalase posi~~e- Hydro_gen per-
branes and nails. Some have a family rustory. In about half of aU cases there I many organisms. In catalase pos1tive orgarusrns ~e
--.-J
an associated immunological disorder such as IDDM, Addison disease, pet . .ala!;e;clestro~:the hydrogen peroxide {produced by the organism) l~vm_g J ' '

nicious anaemia and hypoparathyroidism so that their corresponding fen lllltxoessh'ydl'l(?g-E!I'I peroxide which can be used by the phagocyte (which 15
tures may be superimposed. Humoral immu nity is intact. Treatment consist . .llttiveLaind thus cannot kill the organism- This is in contrast to catalase
of topical and systemic antifungal agents in addition to management of any . .lti\re orgarusms where excess hydrogen peroxide (not catabolised_by cata-
associated endocrine disorder. can be-incorporated into the metabolic pathway of the defective neu-
._,JUJ~-u' or4erto.compensate for its lack of endogenous production so that
-----
·--""
Job syndrome (hyperimmune IgE syndrome) the.organism helps in its own suicide. .
~ltala54~ JpC-Siti1ve organisms include Stnph. aureus, Salmonella, E._ colt,
_ ...........J
Inherited in an autosomal dominant fashion, there is a combined Band T cell ..... - .J

defect. SeJ'1:lm IgE le vels are very high and in addition there is a raisctl man::esans and fungi such as Cll~ and Asper~llus (the ~st 1S _t!'e --- .J

eosinophil count Characteristic featu res consist of coarse facial feature• serious lung disease in CCD). Be familiar ~th the spectrum of inf~~ction­
recurrent skin sepsis witl\ . ab~ess formation (staphylococcal), cltronic dol most common presentation is with severe infections of the skin and
matitis and sinopulmonary disease (lUng abscesses may occur). ~_(often cervical) with abscess fo~on which is often recu~t
libeco-11nes · ·r and suppurative1\lilh time. Lung involvement conslS~
•DI\I!UJino.nioa~~~~~~·•ith · lung abscess formation and empyema. There 1S
Phagocytic disorders especially of small bones. hepatic and perianal abscesses-
These disorders present in the first few months of life. N eutrophil disordou dial't'bc:lea, hepatosplenomegaly and failure to thrive are common. ~
are divided into either qualitative or quantitative abnormalities. (Quantitativ ~DOll obstnKtion is a rticuJar problem especially affecting the gastnc 241
- - - - -- pa -
240 neutrophil defects are described in Chapter 8 .) ureters and sinuses as a result of granuloma formation.
- Inuestigntions: ru.ritic, non-pitting and non~thetnatous comp~red with urtica~. There
be a serpiuinous border and therefore may minuc erythem.a margmatum.
a. Nitrob1ue tetrazolium test (NBl). In this test colourless/yellow NBT iJ pitating ~~are common and include a sudden change m temperature,
reduced to a deep blue colour when exposed to normal neutrophil•
•- _ __,,.,..,tion. stress and infection.
~hich are a b ft:' to produce a respiratory burst during phagocytosis. Thu\
m CGD the NBT remains colourless/yellow. Carriers may have intero
mediate transitions.
brPrsligotions: u asked for an investigation say that you would like to meas-
ure C1INH levels. Tilere are reduced C1INH and C4 levels during an
-3
3
b. Absent chemiluminesence. attack and between attacks. C2 is reduced during an attack but is normal c:
-~ c. ESR ~.oite~-~ised and there are usually raised ~vels of immunoglobu
between attacks. Remember CllNH levels may be normal if there is a tunc-
&lonal problem (in 15%) so also perform a functional assay if in doubt.
::I
0
0
·~ lins G, A and M. . · · t tta k
'Jmrtment consists of the basic principles of resuscitation m an acu e a c
cc
::I '<
f/) - Treatment includes treating the infection adequately with antibiotics and e&peciaUy if the airway is involved. An androgen such as danazol is given
~ surgery. Prophylactic co-trimoxazole is given. Gamma interferon rna~ to increase the synthesis of C11NH. Arttifibrinolytic agents also can be used
reduce the frequency of infections. White cell count transfusions are given (e .g. £-aminoc:aproic acid).
E for life-~atening infections. Consider bone marrow transplant.
~
><
w Glucose-6-phosphate dehydrogenase deficiency

-
INVESTIGATION OF IMMUNOLOGICAL DISORDERS
0 Rarely G6PO deficiency may also affect neutrophil metabolism and functio1~ -.,. may be asked in some questions to list some investigations that you may
'i:

,.!
Cl)
as well as erythrocyte function (see Chapter 8).

Myeloperoxidase deficiency
$ t to carry out in order to make your diagnosis.
Full blood count including white cell differential. Cultures if infection is
~
0.. Autosomal recessive inheritance. ~a deficiency of myeloperoxid~ In Juspected (many immunodeficiencies have typical infections), ESR and
phagocytes. ~ymptorns are generally mild ~u~g no treatment. CRP. '
SplitT. cell subtypes: CD3/CD4/CD8.
Disorders of complement pathway
Complement CH50 is a non-sensitive screening test for the classic com-
The clinical effect depends on which component is m issing. You should hav1 plement pathway. Includ e C3 and C4 in a complement compon~nt ~n.
a rough J;>icture of what you remember of the class ic and alternative pathway1 A reduction in any of these will lead you to perform assays on mdtVldual
of the complement pathway. ln summary, deficiencies in complement com complement components.
ponents Cl-C4 result in increased s~eptibility to infection by encapsulatcJ 4. B cell function can be assessed by measuring immunoglobulin levels IgG,
bacteria (Hf!emaplrilus influewz.ae, Streptococcus pneumonine and so on). There 1
M , A, 0 .and E. B ool function can also be assessed by measuring antibody
also an increased incidence of connective tissue disorders such as SLE (S(~
p roduction responses to antigens such as measuring anti~y lev~ls
~nda?' to immune complexes). Deficiencies in the C5-C9 components resu~
against OTP. In addition isohaemagglutinin levels such as anti-A, anb-B
m an mcreased susce ptibility to neisserial sepsis s uch as meningococcal a 1~
gonococcal infections. may be measured-
Treatment involves prophylaxis (antibiotics and vaccination) and agg~ f. T cell function can be a,ssessed using delayed type hypersensitivity skin
sive treatment of infection . tests against, for example, mumps antigen. Candida antigen and Tetanus
toxoid. A positive skin test makes aT cell abnormality very unlikely. T c~ll
Hereditary angio-oedema p roliferation studies may also be perlormed: here T c~lls are cultured wtth
This is ~clu~ed here as a defect in complement (no immunological featu~) m itogens such as phytohaemagglutinin and the proliferative response
~ented .m ~n. autosomal dominant fashion, it is caused by a deficiency 1• assessed (the latter is significantly reduced in T cell abnormalities).
C1 esrerase inhtbttor (CliN~ usually inhibits the activation of thEt (l
complement component. There are two types: (1) 85% - reduced levels 1
J. Tests of phagocyte function. Nitroblue tetrazolium test (NBT) - see earlier
CliNH; (2) 15%- normal levels but defective function. It is rare before pube1l d escription.
but incre~~ in incidence a fterwards. J, CXR is helpful in the newborn period if one suspects a T cell abnormality
Cl~ically it presents as recu~t episodes of angio-oedema principal! since it may be associated with an absent thymus shadow (e.g. OiGeorge
~ffectin~ the face, extre~ties, airway (hoa.rseness, strido r) and intestine (abdOit syndrome. SCIO). A CXR may also indicate pulmonary infection, a com-
2A2 mal pam, 0 and V, acute abdomen). The angioedema is typically p ainlt mon accompaniment of immunodeficiency -states. 243
. . . . . . . . . hadenopathy and clubbing sometimes complicated_later with an oppor-
AIDS m the paediatric population IS usually acquired by ve rtlcal tTarlSmlSSlO~ ~tic infection. Those children with initial liP presentation have a longer sur-
(~90%). The remainder are accounted for by blood traflSfusion, blood prod· I'll compared to those with an initial opportunistic infection presentation.
ucts such as for leukaemia, sexual activities/abuse and i.v. drug abuse. Blood H!V infection affects the central nervous system causing an encephalopa-
products are now properly screened but children may still be at risk if they y(more commonlv than adults) and can cause failure of brain growth with
re~ei~ed_products.before about 1996. It seems that the v~rtical risk ~f trans- lting microceph~ly. developmental delay and an array of ?t.her neurol~g·
-3
nuss1on IS greater tf the mother has a low CD4 cell count. 1f the baby IS below disturbances with a verv variable expression such as spashc1ty and ataxta. 3
34 weeks' gestation, if the baby is second born (rather than first bom) and il shows characteristic enhancement of the frontal lobes and basal ~anglia c
-; :s
> the baby is born by a vaginal delivery. The vertical transmission rate is esti· lth possible calcification, cerebral atrophy, ventricular enlargement and 0
·~ mated to be about 14%. Breast feeding increases the risk of vertical traflSmis- hfte matter attenuation. CNS tumours are uncommon in paediatric AIDS 0
CQ
:s sion by a further 14°~o. Thus ~abies tend to p~ delivered. by ~aesarean secti~n f. adults) and supra-added infectioflS such as CnJPtococcus may occur. The '<
(/)
an~ parents are adv_ased agamst- b~ast feedmg. lbe latter IS ~~t ~e case ll\ 1\lrse of HIV encephalopathy is \'ery variable. . .
<(
Tiurd World countr1es whe.re the riSk of death .from malnutritiOn IS greate1 Tumours such as the common skin tumour Kaposi sarcoma are rare m chtl-
E than that from AIDS. with AIDS. ·
cu There are manv immunological changes noted in AIDS children and these
>< ude T cell ab~ormalities (decreased CD4 cell count, decreased Il-2 pro-
w

-0
Clinical features of AIDS ion and IFN-y production and decreased proliferative r~p~nses to a~ti­
'i::
It appears that the pattern of illness falls into two separate categories. Babie$ ) and B lymphocyte abnormalities (polydonal B ce~l ac:1vahon r_esulting
.~ who acquired the HIV prenatally appear to have a short incubation periO<! l\ypergammaglobulinaemia, pr~uction of ~utoanhbod1e_s_ ~nd 1mmune
"C
Cl) with symptoms developing at about 4-6 months o£ life. Those who acquired plexes with, for example, a posttrve Coombs test and pos1~ve ANA)._Th~
cu HJV peri-or postnatally tend to have a longer incubation period with symp asect p roduction of autoantibodies is responsible for the mcreased mcl-
a.
toms starting at about 2-3 years. These children account for about 80% of e of autoimmune diseas~ seen in AIDS.
cases and they tend to have a better prognosis.
Infants may come to the attention of paediatridans because of non-specifi<
features such as failure to thriv7'pyrexia of unknown origin, generalised lym·
phadenopathy and/or hepatosplenomegaly (the last two more common than
with adult HIV infection). Other ·non-specific featuxes include parotid gland . . . . .
enlargement, chronic dermatitis, chronic Olrrdida nappy rash as well as per· llble 9.2 Summary of management pnnaples tn paediatriC AIDS . .
sistent oral candidiasis; recurrent otitis media is also common. lllfections Early diagnosis and aggressiv~ tre~tment of_mfect•~ns.
Th resent ·th infecti d to· odefi · B 11 d~ -.nunisations Should receive almost all vaccanat•ons. Not hve poho but
_ey may P Wl • on seco~ ary ~un oency. ce r killed (including co-habitants). No BCG. Should receive
function may present w1th features diSCUssed earlier such as Streptococcus, Pneumovax. influenza vaccination, hepatitis B
Ha.snwphilus and Stap/1. au reus infections and recurrent severe pyogenic infection vaccination. Passive lg if exposed to measles or
is common. These may be severe and recurrent and difficult to treal chickenpox..
Opportunistic infections include Pneunux:ystis jiroveci pneumonia (diagnosed by Antibiotic prophylaxis Co-trirnoxazole is given to HIV in!ected children whe~
bronchiolar lavage and specific Ag staining), Mycobacterium auium-intracellulart ~cell counts dro~ ~~low ~ertam levels as a protection
,..._ d'd ( · · 1 d"d' · ) C
._..n 1 a gastromtestlna can 1 taSIS , ryptospon tum "d" (chro · d' h )
me 1arr oea , ._ idovud.. ) agamst Pneumocyrns)troveet
R
. Standard therapy in
tranS<riptase inhibitor.
•M
Cryptococcus neop,rma ns ( memng•tis
• · · )
and h erpes. sunp
. 1ex . lla zoster ,.. , (z
· an d vance ene everse tHough not started in children who are
children.
infections of the skin. Pneumocystis jiroveci occurs at a relatively early stage ill asymptomatic. Beware bone marrow suppression and
the illness compared to adults with AIDS. In those infants who have a shOJI hepatotoxic:lty side effects. DDI ~dld~xyinosine) and .
incubation period this can even be their presenting illness, which in somr DOC (dideoxycytosine) ~re used 10 chsldren unrespon~•ve
to /(Lf. Use of />Zr durtng pregnancy decreases the nsk
cases can be fa ta1· of HIV transmissidli to baby significantly. Continue
Lymphocytic interstitial pneumonitis (liP) describes a type of chronli postnatally in baby for 6 weeks.
lung disease which is caused by infiltration of the lungs with lymphocyte& ~follow-Up To check for. growth and developmeAt. worsening
and p lasma cells. There are few symptoms--early in the disease. It affecl.l symptoms and side effects of treatment. .
about half of the children affected with HIV infection. The CXR shows bilat ~social support This involves caring for and educating the fam•ly as well
as the child. some of whose members may themselves be
eral reticulonodular s.hadowing. Later in the disease the children .may devel HIV positive. Assessment of coping strategies. Ultimately
244- op gradually increasi111g dyspnoea, cough. wheeze, hypoxaemia, mediastinul terminal care. 245
10
Investigation of AIDS
-Anti-HI~ IgG _(b~ ELISA and confirmed by Western blot techniques):
problem of tdentlfymg these antibodies in the infant is that it is possible
the baby may have acquired them from the mother through the plact~
etabolic

:rnese antibodies ca_n last for 18 months. Thus detection of the antibody iJ\
mfant only after this age makes the diagnosis positive. The presence of a
HIV. IgA anti~ies_ (which cannot cross the placenta) is also a meth01l
1seases
-~ making a pos1tive d1agnosis.
-Polymerase cllllin reaction is a method of HN DNA amplification and ~
·~ method used to detect HIV virus in the blood.
:I
Cl) - P24 antigen detection can be used.
~
- V!ral culture of white cells remains the gold standard for detection of
E
ca
VIruS.
"' this chapter we will cover the cqmmoner metabo.lic disorders that are fre-
>< q'jiently asked about in the e~tion as well as some of the rarecQ!les th~t
w Management of AIDS
ite also exam favourites.
-
u
'i:
.~
"'0
C1)
ca
This involves many as.pects as shown in Table 9.2.. Although direct questioning about inborn errors of metabolism is relatively
rtre some knowledge about the commoner disorders is expected, and have
in)e_up in the grey cases and data interpretation questions in the past. In addi-
dbn, the presentation and management of such disorders could well be asked
c.. lbo~. in the dini£al ex~m.ID~tion. You should have a ~nce...to ~im_plifi:<l
lletabolic path"'-"ays as you read throt!gh U:te inl?9m eUQ.ts..QL_ll).etab_9Jbsm.

Causes
1. ~aline depletion hyponatra~ia ·
ObviouSFysfmulfane~Soa~r ~~~~ not aff~t eJa~m
(Oncentration. However whenVOU!ne depletion is sufficient to cause A~
ltlease then water retention will lead ~~hU?onatraemia (overriding osm.2_tic
(OnttQ!). In renal causes of~&!!.~ the~ response is o.ftenjnadeqllate and
an incr.eB..S~ in volume is a~d byJ:hii'St.aru:tdti!}l<_lng.
~ ~fu"lg, ~iarrhoea, i!!testinal~, s~~xcess diur~~s,
adrenal insufficie~cy and ren<Jl~. Clinical sigils :will be those of vol-
-~ d~I?Jetion and treatment will inv.olve.tlui~Rt<u:ement.

3. Dil~onal hl20_~~'!!_mia
!here is mes~nce an excess of water. This-may be due to excess ADH pro-
duction or a re5ult of renal inability to dilute urine.
-~Excessive fluid intake (raft), re~l failure, c:aqiiac failure, c~is,
~hrotic :f;';drome, ia,tto,.unic ~~toni5_!9,.t;!:~n, s:mdn>me of
tna.RR_rop~~n (S.&Ylli). SJADH is caused by: I~
{e.g: pneu.:morua, venfi:I'!tion); CNS disease (e.g. trauma, meningoenc.e.phali-
tis. twriour}!_ gain (e.g.~~to~rative); ~ (e.g. chlo[ll[Q~de...-carba-
246 mazepine, morplime,_rifampicin, vinqi&tine). Ec_!g~production is rare. 247
The general treatment of dilutio~l hyponatraemia involves flllli~,!e'Str·icti41P~::I:~I!l]~Jl'!·······················

+<U
:E
but if fluid overloaded ix. mannitol can induce a diuresis and e liminate wa,ll•lll:~; ly presents as w eakness, pa ralytic iletus, urinary retention (both sec-
For a detailed description of SIAOH see Ctiapter 7 .

3. Incr~ased number of osmoles in the plasma


-

For example,·glucose. This increases the extracellular fluid (ECF) osrno!lall~


to effects on smooth muscle), polyurria and metabolic alkalosis (see
2 for ECG cha~ges).

::1 causing 'water to pass into the ECF from the ICF.decreasing the ECF
(!)
->cu concentration. In addition to this, the increase of ADH caused by the
load causes water retention with a CQrresponding fall in aldosteron e
tion and a natriuresis.
·~
a. Re11al: diuretics, osm_otic diuresis (e.g. gllycosuria), hyperaldosteronis~,
::1
f/) 4. Pseudohyponatraemia
' ren al tubular acidosis.
<( 1h.i.s is where there "is hyperproteinaemia or hyperlipidaernia that n ....-....,.01.... b. Gastroi11testinal: vomiting, diarrhoea, )aXI(ative abuse, villous adenoma
the fractional water content of plasma. (which produces a lot of mucus).
E
cu The plasma osmolality will thus be increased in cause (3), will be Movement of potassium into the cell: insullin administration (or following
><
w in·cause (4) and reduced in causes (1) and (2). In (1) there will be signs a glucose infusion), metabolic alkalosis, caltecholamines, drugs such as

"' -
....
2
.~
"0
<U
cu
volume d epletion, in SIADH there will be a norma l ECF volume and in
other dilutio~al causes there will be an increase in ECF volume (raised
oedema, ascites and pulmonary oedema).
. NB Osmo larity is calculated-and osmolality is measured.
(mOsmql/kg) = 2 x (Na + K) + urea + glucose. If the m easured osmol•
sa1butamol infusion .

potassium excretion is useful to know • since a urinary potassium excre-


of more than 20 mmol/1 potassium inllplies renal loss, and a urinary
less than this l~s implies extrarenal Uosses. Treat the underlying cause
a. lity is significantly greater than the osmolarity (e .g. by 10 mOsm or- ~ve potassium supplements.
referred to as an osmolar gap, then one should suspect that there
osmotically active components other than those mentioned in the abo\
equation.
ri ..·h"·tir:.tlr·~oJJ~nically presents as weakness and card"ac arrhythmias (see Chapter 2 for
Sodium deficit in an individual with hyponatraemic
changes).
(not in dilutional 'hyponatraemia) may-be calculated by the
equation:
- Sodiull,l deficit = 0.6 x body weight (kg) x (normal plasma sodium, It
135- patient's plasma sodium). Reduced renal excretion: Renal failure, h}'YPoaldosteronism (Addison dis-
ease), potassium-sparing diuretics (e.g. spiironolactone), hypovolaernia.
-The mmol required to raise the plasma sodium by X mmol/1 (acutely) =
x body weight x rise wanted in mmol/1. Beware o f acidosis during Movement out of cells: Hypoinsulinis,!lln acidosis, rapid cell lysis (e.g.
correction. tumour lysis syndrome), trauma and bumlS.
Increased intake, in particular if there is atbnormal renal function.
Eti',;rll[i]::!aiJi~~~·····················lrseud~hyperkalaemia: Leaving cuff on anm for too long before venepunc-
ture. Haemolysis if there is a difficult vemepuncture or if the needle is too
Causes
small. Stored blood.
- Isolate<!. wat~pleti<_?n: diabetes~ipidius ltatment consists of treating the underlyins; cause and stabilising the heart
- Iatrog~.Pic: via hypematraemic i~_ infusions and drugs lllth calcium gluconate, using bicarbonate~ or insulin/glucose infusions,
-Conn syndrQ.!.!le (with low potassium) '
.,utamol nebulisers/infusions, exchange ~ins, diure~cs and dialysis.
-Combined water an_9 sodium loss-With water Joss predominating.
It is important to remember that signs of volume d~pletion will not be
obvious as they are in _!lyponatraemic dehydration since there is a shift
flu~d from the l~heECF and thus weight loss is the most reliable Y,1h presentation of l~rgy, poor ~~rfu~n and a metabolic aci-
248 ca!or. The skin m ay have _i'doughy' texture. in a neonate should immediately lead I you to think of the three most 249
I
likely causes which are: sepsis, c~ngenita~ heart disease arid a metaQ<>lic 'II!Ta , ~b~l~e~.~1o~f1~~C~on~t~in:_::u~e~d:__ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __

+:E
C1)
on:ter. Remember that the presence o( a metabolic acidosis together " tnbom error of
hypoglycaemia should strongly suggest to you a metabolic disorder. Sef metabolism: MetaboliC

hyperglycaemia. 1

In any metabolic disorder you should look for clues in the history such ~em.la:
-Organic
rbo 1
c.a xy ase
.

Propiony1 coA AR
Acute
.

• •tn h en·ta~'e
Investigation
commonly produces a metabolic acidosis but is usually accompanied tJCp~a~m~p~l~