D DDR RR D DDe eex xxt tte eer rr M MMD DD F FFR RRC CC P PPA AAT TTH HH

S SSG GGU UUS SSO OOM MM G GGR RRE EEN NNA AAD DDA AA ( ((W WW. ..I II) ))
I IIn nnt ttr rro ood ddu uuc cct tti iio oon nn
N NNe eeo oon nna aat tta aal ll a aag gge ee f ffi iir rrs sst tt 4 44 w wwe eee eek kks ss a aaf fft tte eer rr b bbi iir rrt tth hh
I IIn nnf ffa aan nnc ccy yy 1 11
s sst tt
y yye eea aar rr
E EEa aar rrl lly yy c cch hhi iil lld ddh hho ooo ood dd 1 11- --4 44 y yye eea aar rrs ss
L LLa aat tte ee c cch hhi iil lld ddh hho ooo ood dd 5 55- --1 114 44 y yye eea aar rrs ss
C CCa aau uus sse ees ss o oof ff D DDe eea aat tth hh b bby yy A AAg gge ee
C CCa aau uus sse ees ss R RRa aat tte ee
( (( n nno oo. .. o oof ff d dde eea aat tth hhs ss p ppe eer rr 1 110 000 00, ,,0 000 000 00 p ppo oop ppu uul lla aat tti iio oon nn) ))
U UUn nnd dde eer rr 1 11 y yye eea aar rr
P PPe eer rri iin nna aat tta aal ll c cco oon nnd ddi iit tti iio oon nns ss ( (( I IIU UUG GGR RR/ //L LLB BBW WW, ,, R RRD DDS SS, ,, b bbi iir rrt tth hh a aas ssp pph hhy yyx xxi iia aa, ,, b bbi iir rrt tth hh t ttr rra aau uum mma aa ) )) 692
C CCo oon nng gge een nni iit tta aal ll a aan nno oom mma aal lli iie ees ss
S SSI IID DDS SS
P PPn nne eeu uum mmo oon nni iia aa
1 11- --4 44 y yye eea aar rr s ss 43.3
I IIn nnj jju uur rri iie ees ss
C CCo oon nng gge een nni iit tta aal ll a aan nno oom mma aal lli iie ees ss
M MMa aal lli iig ggn nna aan nnt tt n nne eeo oop ppl lla aas ssm mms ss
H HHo oom mmi iic cci iid dde ee
H HHe eea aar rrt tt d ddi iis sse eea aas sse ees ss
5 55- --1 114 44 y yye eea aar rrs ss 37
I IIn nnj jju uur rri iie ees ss
M MMa aal lli iig ggn nna aan nnt tt n nne eeo oop ppl lla aas ssm mms ss
C CCo oon nng gge een nni iit tta aal ll a aan nno oom mma aal lli iie ees ss
H HHo oom mmi iic cci iid dde ee
H HHe eea aar rrt tt d ddi iis sse eea aas sse ees ss
B BBi iir rrt tth hh I IIn nnj jju uur rri iie ees ss
B BBr rro ooa aad dd t tte eer rrm mm t tth hha aat tt s ssp ppa aan nns ss t tth hhe ee s ssp ppe eec cct ttr rru uum mm o oof ff
m mme eec cch hha aan nni iic cca aal ll t ttr rra aau uum mma aa t tto oo a aan nno oox xxi iic cc d dda aam mma aag gge ee. ..
O OOc ccc ccu uur rr i iin nn a aab bbo oou uut tt 5 55/ //1 110 000 000 00 l lli iiv vve ee b bbi iir rrt tth hhs ss. ..
P PPr rre eed ddi iis ssp ppo oos ssi iin nng gg f ffa aac cct tto oor rrs ss
C CCe eep pph hha aal llo oop ppe eel llv vvi iic cc d ddi iis ssp ppr rro oop ppo oor rrt tti iio oon nn
D DDi iif fff ffi iic ccu uul llt tt l lla aab bbo oor rr ( ((B BBr rre eee eec cch hh p ppr rre ees sse een nnt tta aat tti iio oon nn) ))
p ppr rre eem mma aat ttu uur rri iit tty yy
B BBi iir rrt tth hh I IIn nnj jju uur rri iie ees ss
C CCr rra aan nni iia aal ll i iin nnj jju uur rri iie ees ss
C CCa aap ppu uut tt s ssu uuc ccc cce eed dda aan nne eeu uum mm
C CCe eep pph hha aal llo ooh hhe eem mma aat tto oom mma aa
S SSk kku uul lll ll f ffr rra aac cct ttu uur rre ees ss
I IIn nnt ttr rra aac ccr rra aan nni iia aal ll h hhe eem mmo oor rrr rrh hha aag gge ee
P PPe eer rri iip pph hhe eer rra aal ll n nne eer rrv vve ee i iin nnj jju uur rri iie ees ss
B BBr rra aac cch hhi iia aal ll p ppa aal lls ssy yy
F FFa aac cci iia aal ll n nne eer rrv vve ee p ppa aal lls ssy yy
F FFr rra aac cct ttu uur rre ees ss
C CCl lla aav vvi iic ccl lle ee
h hhu uum mme eer rru uus ss
R RRu uup ppt ttu uur rre ee o oof ff t tth hhe ee l lli iiv vve eer rr
C CCo oon nng gge een nni iit tta aal ll A AAn nno oom mma aal lli iie ees ss
M MMo oor rrp pph hho ool llo oog ggi iic cc d dde eef ffe eec cct tts ss t tth hha aat tt a aar rre ee p ppr rre ees sse een nnt tt a aat tt b bbi iir rrt tth hh, ,,
b bbu uut tt m mma aay yy n nno oot tt b bbe eec cco oom mme ee c ccl lli iin nni iic cca aal lll lly yy a aap ppp ppa aar rre een nnt tt u uun nnt tti iil ll
l lla aat tte eer rr l lli iif ffe ee. ..
M MMa aay yy h hha aav vve ee a aa g gge een nne eet tti iic cc o oor rri iig ggi iin nn b bbu uut tt c cca aan nn b bbe ee d ddu uue ee t tto oo o oot tth hhe eer rr
f ffa aac cct tto oor rrs ss. ..
P PPE EED DDI IIA AAT TTR RRI IIC CC P PPA AAT TTH HHO OOL LLO OOG GGY YY
C CCo oon nng gge een nni iit tta aal ll A AAn nno oom mma aal lli iie ees ss
I IIm mmp ppo oor rrt tta aan nnc cce ee
I IIm mmp ppo oor rrt tta aan nnt tt c cca aau uus sse ee o oof ff i iin nnf ffa aan nnt tt m mmo oor rrt tta aal lli iit tty yy
3 33% %% o oof ff n nne eew wwb bbo oor rrn nns ss h hha aav vve ee a aa m mma aaj jjo oor rr m mma aal llf ffo oor rrm mma aat tti iio oon nn
w wwh hhi iic cch hh h hha aas ss e eei iit tth hhe eer rr c cco oos ssm mme eet tti iic cc o oor rr f ffu uun nnc cct tti iio oon nna aal ll
s ssi iig ggn nni iif ffi iic cca aan nnc cce ee. ..
B BBy yy t tth hhe ee e een nnd dd o oof ff i iin nnf ffa aan nnc ccy yy, ,, t tth hhe ee i iin nnc cci iid dde een nnc cce ee o oof ff m mma aaj jjo oor rr
m mma aal llf ffo oor rrm mma aat tti iio oon nns ss a aap ppp ppr rro ooa aac cch hhe ees ss 1 110 00% %%. ..
3 330 00- --4 440 00% %% o oof ff a aad ddm mmi iis sss ssi iio oon nns ss t tto oo p ppe eed ddi iia aat ttr rri iic cc h hho oos ssp ppi iit tta aal lls ss a aar rre ee
d ddu uue ee t tto oo d ddi iis sse eea aas sse ee a aar rri iis ssi iin nng gg f ffr rro oom mm c cco oon nng gge een nni iit tta aal ll
m mma aal llf ffo oor rrm mma aat tti iio oon nns ss. ..
E EEt tti iio ool llo oog ggy yy
G GGe een nne eet tti iic cc
K KKa aar rry yyo oot tty yyp ppi iic cc
a aab bbn nno oor rrm mma aal lli iit tti iie ees ss
S SSi iin nng ggl lle ee g gge een nne ee
m mmu uut tta aat tti iio oon nns ss
E EEn nnv vvi iir rro oon nnm mme een nnt tta aal ll
M MMu uul llt tti iif ffa aac cct tto oor rri iia aal ll
P PPa aat tth hho oog gge een nne ees ssi iis ss
C CCo oom mmp ppl lle eex xx a aan nnd dd s sst tti iil lll ll p ppo ooo oor rrl lly yy u uun nnd dde eer rrs sst tto ooo ood dd
G GGe een nne eer rra aal ll p ppr rri iin nnc cci iip ppl lle ees ss
1 11 . .. T TTi iim mmi iin nng gg o oof ff t tth hhe ee p ppr rre een nna aat tta aal ll i iin nns ssu uul llt tt h hha aas ss a aan nn i iim mmp ppo oor rrt tta aan nnt tt
i iim mmp ppa aac cct tt o oon nn b bbo oot tth hh t tth hhe ee o ooc ccc ccu uur rrr rre een nnc cce ee a aan nnd dd t tth hhe ee t tty yyp ppe ee o oof ff
m mma aal llf ffo oor rrm mma aat tti iio oon nn p ppr rro ood ddu uuc cce eed dd. ..
2 22 . .. G GGe een nne ees ss t tth hha aat tt r rre eeg ggu uul lla aat tte ee m mmo oor rrp pph hho oog gge een nne ees ssi iis ss m mma aay yy b bbe ee t tth hhe ee
t tta aar rrg gge eet tt o oof ff t tte eer rra aat tto oog gge een nns ss. ..
H HHO OOX XX g gge een nne ees ss
A AAb bbn nno oor rrm mma aal lli iit tti iie ees ss i iin nn M MMo oor rrp pph hho oog gge een nne ees ssi iis ss
M MMa aal llf ffo oor rrm mma aat tti iio oon nns ss
D DDe eef ffi iin nni iit tti iio oon nn
P PPr rri iim mma aar rry yy s sst ttr rru uuc cct ttu uur rra aal ll a aab bbn nno oor rrm mma aal lli iit tty yy w wwi iit tth hh p ppo ooo oor rr
f ffo oor rrm mma aat tti iio oon nn o oof ff t tti iis sss ssu uue ee d ddu uue ee t tto oo a aa l llo ooc cca aal lli iiz zze eed dd e eer rrr rro oor rr t tth hha aat tt
o ooc ccc ccu uur rrs ss d ddu uur rri iin nng gg d dde eev vve eel llo oop ppm mme een nnt tt. ..
I IIn nnt ttr rri iin nns ssi iic cca aal lll lly yy a aab bbn nno oor rrm mma aal ll d dde eev vve eel llo oop ppm mme een nnt tta aal ll p ppr rro ooc cce ees sss ss. ..
M MMo oos sst tt c cch hhi iil lld ddr rre een nn a aar rre ee o oot tth hhe eer rrw wwi iis sse ee n nno oor rrm mma aal ll a aap ppa aar rrt tt f ffr rro oom mm
t tth hhe ee d dde eef ffe eec cct tt. ..
Malformations Malformations - - examples examples
Polydactyly & Syndactyly Polydactyly & Syndactyly
Cleft lip Cleft lip
Cleft palate Cleft palate
Congenital heart disease Congenital heart disease
Disruption Disruption
Structural defect caused by secondary Structural defect caused by secondary
destruction of or interference with a previously destruction of or interference with a previously
normally formed part. normally formed part.
Arise from an extrinsic disturbance in Arise from an extrinsic disturbance in
morphogenesis morphogenesis
Disruption Disruption - - Mechanisms Mechanisms
Entanglement followed by Entanglement followed by
the tearing apart or the tearing apart or
amputation of a normally amputation of a normally
developed structure by developed structure by
strands of amnion floating strands of amnion floating
within amniotic fluid. within amniotic fluid.
Interruption of blood supply Interruption of blood supply
to a developing part leading to a developing part leading
to infarction, necrosis, to infarction, necrosis,
and/or resorption of and/or resorption of
structures distal to the insult. structures distal to the insult.
Deformation Deformation
Localized or generalized compression of the Localized or generalized compression of the
growing fetus by abnormal biomechanical growing fetus by abnormal biomechanical
forces. forces.
Arises later in fetal life than do malformations. Arises later in fetal life than do malformations.
Factors Factors Maternal Maternal Fetal Fetal
First pregnancy First pregnancy Multiple fetuses Multiple fetuses
Small uterus Small uterus Oligohydramnios Oligohydramnios
Leiomyomas Leiomyomas Abnormal presentation Abnormal presentation
Sequence Sequence
Multiple congenital anomalies that result from Multiple congenital anomalies that result from
secondary effects of a single localized aberration secondary effects of a single localized aberration
in organogenesis. in organogenesis.
Initiating event may be malformation, Initiating event may be malformation,
deformation or disruption. deformation or disruption.
Mechanism of Sequence Formation Mechanism of Sequence Formation
Examples of Sequences Examples of Sequences
Potter sequence. Potter sequence.
Amniotic band disruption sequence. Amniotic band disruption sequence.
Breech deformation sequence. Breech deformation sequence.
Potter Sequence Potter Sequence
Oligohydramnios (= lack of amniotic fluid) due to: Oligohydramnios (= lack of amniotic fluid) due to:
Renal agenesis/ Renal agenesis/ maldevelopment maldevelopment
Amniotic fluid leak Amniotic fluid leak
Uteroplacental insufficiency Uteroplacental insufficiency
Potter Sequence Potter Sequence
Oligohydramnios causes Oligohydramnios causes
Pulmonary hypoplasia Pulmonary hypoplasia
Amnion nodosum Amnion nodosum
Fetal compression Fetal compression
Worsens pulmonary hypoplasia Worsens pulmonary hypoplasia
Breech presentation Breech presentation
Altered facies Altered facies
Positioning defects of feet and hands Positioning defects of feet and hands
Amnion Nodosum Amnion Nodosum
Potters Facies Potters Facies Malformation Syndromes Malformation Syndromes
The presence of The presence of > >1 developmental anomalies of 1 developmental anomalies of
> >2 systems due to a common etiology 2 systems due to a common etiology
With two exceptions, none of these disorders With two exceptions, none of these disorders
occurs more frequently than 1:3,000 births occurs more frequently than 1:3,000 births
Those two exceptions are: Those two exceptions are:
Down syndrome Down syndrome - - 1:660 1:660
XXY syndrome XXY syndrome - - 1:500 males 1:500 males
Prematurity and Intrauterine Growth Prematurity and Intrauterine Growth
Retardation (= IUGR) Retardation (= IUGR)
Gestational Age Gestational Age
Term: 38 Term: 38- -42 weeks gestational age (= GA). 42 weeks gestational age (= GA).
Preterm: <37 weeks GA. Preterm: <37 weeks GA.
Post term: >42 weeks GA. Post term: >42 weeks GA.
Growth Chart Growth Chart
Appropriate for gestational Appropriate for gestational
age (= AGA): Birth weight age (= AGA): Birth weight
between 10th and 90th between 10th and 90th
percentile for GA. percentile for GA.
Small for gestational age (= Small for gestational age (=
SGA): Birth weight below SGA): Birth weight below
10th percentile for GA. 10th percentile for GA.
Large for gestational age (= Large for gestational age (=
LGA): Birth weight above LGA): Birth weight above
90th percentile for GA. 90th percentile for GA.
If All of These Infants Are the Same If All of These Infants Are the Same
Gestational Age, Which One IS AGA, SGA, Gestational Age, Which One IS AGA, SGA,
and LGA? and LGA?
Premature Premature
<37 weeks GA. <37 weeks GA.
Low Low- -birth weight (LBW) infants: birth weight (LBW) infants: < <2,500 g at 2,500 g at
birth birth
Premature Premature
and/or and/or
IUGR for their gestational age AKA SGA. IUGR for their gestational age AKA SGA.
Very low birth weight (VLBW) infants: <1,500 Very low birth weight (VLBW) infants: <1,500
g. g.
Extremely low birth weight (ELBW) infants: Extremely low birth weight (ELBW) infants:
<1,000 g. <1,000 g.
AKA immature. AKA immature.
IUGR IUGR
Fetal causes Fetal causes symmetric IUGR symmetric IUGR
Chromosomal disorders Chromosomal disorders
Congenital malformations Congenital malformations
Congenital infections Congenital infections
Placental causes Placental causes asymmetric IUGR asymmetric IUGR
Placenta previa Placenta previa
Placental abruption Placental abruption
Placental infarction Placental infarction
Maternal causes Maternal causes - - asymmetric IUGR asymmetric IUGR
Toxemia of pregnancy Toxemia of pregnancy
Chronic hypertension Chronic hypertension
Alcoholism, narcotic abuse and smoking Alcoholism, narcotic abuse and smoking
Evaluation Of The Infant At Delivery Evaluation Of The Infant At Delivery
The The Apgar Apgar Score Score
Devised by Dr. Virginia Devised by Dr. Virginia Apgar Apgar. .
Simple method of determining the chances of Simple method of determining the chances of
survival of a newborn infant by assessing its survival of a newborn infant by assessing its
physiologic condition and responsiveness. physiologic condition and responsiveness.
Predicts perinatal morbidity. Predicts perinatal morbidity.
Not a reliable indicator of long Not a reliable indicator of long- -term term neurologic neurologic
outcome. outcome.
The The Apgar Apgar Score Score
Measurement and Scoring Measurement and Scoring
Sign Sign Score Score
0 0 1 1 2 2
Heart rate Heart rate Absent <100 > Absent <100 >100 100
Respiratory effort Respiratory effort Absent Slow, irregular Good, crying Absent Slow, irregular Good, crying
Muscle tone Muscle tone Limp Some flexion Active motion Limp Some flexion Active motion
of extremities of extremities
Color Color Blue Body pink, Pink all over Blue Body pink, Pink all over
extremities blue extremities blue
Response to Response to None Grimace Cough or None Grimace Cough or
catheter in throat catheter in throat sneeze sneeze
(tested after oropharynx is clear) (tested after oropharynx is clear)
Apgar Apgar Score Score
Interpretation Interpretation
Evaluated at 1 or 5 minutes. Evaluated at 1 or 5 minutes.
Maximum score = 10. Maximum score = 10.
Correlation between score and mortality during Correlation between score and mortality during
first 28 days of life is very good: first 28 days of life is very good:
Mortality = 0 when score (5 min) Mortality = 0 when score (5 min) > >7. 7.
Mortality = 20% when score (5 min) = 4. Mortality = 20% when score (5 min) = 4.
Mortality = 50% when score (5 min) = 0 Mortality = 50% when score (5 min) = 0- -1. 1.
Complications of Prematurity Complications of Prematurity
Hyaline membrane disease ( Respiratory distress Hyaline membrane disease ( Respiratory distress
syndrome) syndrome)
Necrotizing Enterocolitis Necrotizing Enterocolitis
Intraventricular and germinal matrix hemorrhage Intraventricular and germinal matrix hemorrhage
Respiratory Distress Syndrome (RDS)
AKA Hyaline Membrane Disease AKA Hyaline Membrane Disease
Formation of membranes in the peripheral Formation of membranes in the peripheral
airspaces. airspaces.
Leading cause of morbidity and mortality among Leading cause of morbidity and mortality among
premature infants premature infants
Accounts for half of all neonate deaths in USA. Accounts for half of all neonate deaths in USA.
Pathogenesis Pathogenesis
Prematurity Prematurity
Perinatal asphyxia Perinatal asphyxia
Maternal diabetes Maternal diabetes
Cesarean section before onset of labor Cesarean section before onset of labor
Twin gestation Twin gestation
Male sex Male sex
Pathogenesis Pathogenesis
Clinical features Clinical features
Usually appear normal at Usually appear normal at
birth birth
Within few minutes to Within few minutes to
hours develop a labored, hours develop a labored,
grunting respiration that grunting respiration that
progressively worsens. progressively worsens.
Display a typical X Display a typical X- -ray ray
image of ground glass image of ground glass
alterations of the lungs alterations of the lungs
Pathology Pathology - - gross gross
Lungs are firm and Lungs are firm and
resemble liver more than resemble liver more than
lungs lungs
Microscopy Microscopy
Uneven air expansion pattern with atelectatic Uneven air expansion pattern with atelectatic
alveoli and dilated bronchioles and alveolar alveoli and dilated bronchioles and alveolar
ducts ducts
Scattered foci of alveolar hemorrhage and Scattered foci of alveolar hemorrhage and
edema edema
Microscopy Microscopy
Smooth homogenous Smooth homogenous
pink membranes lining pink membranes lining
terminal and respiratory terminal and respiratory
bronchioles and alveolar bronchioles and alveolar
ducts ducts
Composed of necrotic Composed of necrotic
alveolar lining cells, alveolar lining cells,
plasma plasma transudate transudate, ,
inhaled amniotic fluid inhaled amniotic fluid
including including squames squames and and
fibrin, if hemorrhage is fibrin, if hemorrhage is
present. present.
May be seen in infants who die as early as 3 May be seen in infants who die as early as 3- -4 4
hours after birth hours after birth
Are uniformly present as well formed structures Are uniformly present as well formed structures
by 12 by 12- -24 hours in infants with RDS 24 hours in infants with RDS
In absence of severe disease, at 36 In absence of severe disease, at 36- -48 hours the 48 hours the
membrane begins to organize and separate from membrane begins to organize and separate from
the underlying wall to be replaced by alveolar the underlying wall to be replaced by alveolar
lining cells or bronchiolar cuboidal or columnar lining cells or bronchiolar cuboidal or columnar
cells cells
Treatment Treatment
Ventilatory support Ventilatory support
Surfactant replacement therapy Surfactant replacement therapy
Long term sequelae Long term sequelae
Neurological abnormalities Neurological abnormalities
Chronic lung disease Chronic lung disease
Bronchopulmonary dysplasia Bronchopulmonary dysplasia
Extensive interstitial lung fibrosis Extensive interstitial lung fibrosis Honeycomb lung Honeycomb lung
Bronchopulmonary dysplasia Bronchopulmonary dysplasia
Multifactorial etiology Multifactorial etiology
Primary anoxic injury Primary anoxic injury
Exposure to high concentration of oxygen Exposure to high concentration of oxygen
Positive pressure ventilation Positive pressure ventilation
Pathology Pathology
Hyperplasia and Hyperplasia and
squamous metaplasia of squamous metaplasia of
bronchial epithelium bronchial epithelium
Peribronchial fibrosis Peribronchial fibrosis
Fibrotic obliteration of Fibrotic obliteration of
bronchioles bronchioles
Over distended alveoli. Over distended alveoli.
CASE: A newborn girl is born at 34 weeks and
weighs 2200 gm.
Her Apgars are 7 and 8.
Within hours of birth, girl develops
tachypnea, nasal flaring, intercostal
retractions and grunting. Her skin is
somewhat mottled and lips are dusky.
Chest X Chest X- -ray ray
chest radiograph
demonstrates a bell
shaped thorax with
diffuse and
symmetrical ground
glass infiltrates.
Neonatal Necrotizing Enterocolitis (NEC) Neonatal Necrotizing Enterocolitis (NEC)
Disease of premature infants along with term Disease of premature infants along with term
infants of low birth weights (small for infants of low birth weights (small for
gestational age) gestational age)
Most frequent preoperative diagnosis of infants Most frequent preoperative diagnosis of infants
going to surgery from NICU going to surgery from NICU
Mortality of 25 Mortality of 25- -50% 50%
Clinical Features Clinical Features
Preterm or SGA infant with Preterm or SGA infant with
history of asphyxia requiring history of asphyxia requiring
ventilation develops signs of ventilation develops signs of
obstruction after oral obstruction after oral
feedings have begun feedings have begun
Abdominal distension, Abdominal distension,
bloody stools, shock, DIC bloody stools, shock, DIC
progressing to death progressing to death
Diagnosis Diagnosis
Abdominal radiographs show Abdominal radiographs show
dilated loops of bowel dilated loops of bowel
Pneumo Pneumo peritoneum peritoneum
Pathology Pathology
Typically involves Typically involves
terminal ileum, terminal ileum, caecum caecum
and right colon and right colon
Gross Gross involved bowel involved bowel
distended with small sub distended with small sub
mucosal and serosal mucosal and serosal
collections of air collections of air
Bowel wall thin and Bowel wall thin and
delicate with spotty areas delicate with spotty areas
of necrosis and possible of necrosis and possible
perforation. perforation.
Microscopy Microscopy
Mucosal coagulative Mucosal coagulative
necrosis extending into necrosis extending into
and often through the and often through the
submucosa and muscular submucosa and muscular
layers layers
Small air filled spaces Small air filled spaces
beneath mucosa beneath mucosa
pneumatosis pneumatosis intestinalis intestinalis
Treatment Treatment
Avoid feeding, Avoid feeding,
Decompress abdomen (insert NG tube) Decompress abdomen (insert NG tube)
IV fluids IV fluids
Treat shock Treat shock
Antibiotics Antibiotics
Avoid surgery unless signs of perforation Avoid surgery unless signs of perforation
complications complications
Early Early sepsis, shock, acute tubular necrosis, sepsis, shock, acute tubular necrosis,
DIC, intestinal perforation DIC, intestinal perforation
Delayed Delayed short gut syndrome, short gut syndrome, malabsorption malabsorption, ,
strictures, atresia, obstruction, fistula etc. strictures, atresia, obstruction, fistula etc.
Lets return to the same case. Her RDS was
treated with typical ventilatory support and she
is now only on supplemental oxygen by nasal
canula. She begins oral feeding and develops
vomiting, blood tinged diarrhea and a distended
abdomen.
Cause of her present problem?
Neonatal Intraventricular Neonatal Intraventricular
hemorrhage hemorrhage
Bleeding into the germinal matrix with extension Bleeding into the germinal matrix with extension
into ventricles and beyond into ventricles and beyond
Germinal Matrix Germinal Matrix source of nerve cells in source of nerve cells in
embryo and fetuses (up to 33 weeks of embryo and fetuses (up to 33 weeks of
gestation.) gestation.)
Richly vascular area with many thin walled Richly vascular area with many thin walled
capillaries that are very sensitive to anoxia capillaries that are very sensitive to anoxia
Grading Grading - - Pathology Pathology
I I Hemorrhage restricted to germinal matrix. Hemorrhage restricted to germinal matrix.
II II Intraventricular extension of hemorrhage Intraventricular extension of hemorrhage
without dilatation. without dilatation.
III III - - Intraventricular extension of hemorrhage Intraventricular extension of hemorrhage
with dilatation. with dilatation.
IV IV Intraventricular and Intraventricular and Intraparenchymal Intraparenchymal
hemorrhage hemorrhage
Pathology Pathology
Evolution and sequelae Evolution and sequelae
Rapid death if massive hemorrhage with tears of Rapid death if massive hemorrhage with tears of
falx falx cerebri cerebri or or tentorium tentorium
In long term survivors In long term survivors cavitations or cavitations or
pseudocysts surrounded by hemosiderin laden pseudocysts surrounded by hemosiderin laden
macrophages and gliosis. macrophages and gliosis.
Hydrocephalus seen in 10 Hydrocephalus seen in 10- -15% of survivors 15% of survivors
LETS AGAIN RETURN TO THE CASE OF
BABY GIRL.
She recovers from necrotizing enterocolitis and now has been
intubated and is being ventilated.
Subsequently she acutely develops:
- apnea and bradycardia
- turns pale
- and develops a seizure
Physical examination now shows a bulging anterior
fontanelle and the lab studies several hours later exhibited
anemia.
WHAT MAY HAVE HAPPENED?
Neonatal Jaundice Neonatal Jaundice
2 main types 2 main types
Physiological jaundice Physiological jaundice
Pathological jaundice Pathological jaundice
Clinical estimation of Jaundice Clinical estimation of Jaundice
Detected by blanching the skin with digital pressure Detected by blanching the skin with digital pressure
Bilirubin level > 5 mg/dl Bilirubin level > 5 mg/dl clinical manifestation. clinical manifestation.
Physiological Jaundice Physiological Jaundice
Elevated unconjugated bilirubin during first Elevated unconjugated bilirubin during first
week of life. week of life.
2 functionally distinct periods 2 functionally distinct periods
Phase I Phase I lasts 5 days in term infants and 7 days in lasts 5 days in term infants and 7 days in
preterm infants. preterm infants.
Serum bilirubin level may reach 12 Serum bilirubin level may reach 12- -15 mg/dl 15 mg/dl
Phase II Phase II decline of serum bilirubin levels , lasts for decline of serum bilirubin levels , lasts for
2 weeks. 2 weeks.
After this normal adult values are reached. After this normal adult values are reached.
Pathological Jaundice Pathological Jaundice
Any of the following features characterize Any of the following features characterize
pathological jaundice pathological jaundice
Clinical jaundice appearing in first 24 hours Clinical jaundice appearing in first 24 hours
Total bilirubin > 15 mg/dl ( Hyperbilirubinemia) Total bilirubin > 15 mg/dl ( Hyperbilirubinemia)
Conjugated bilirubin > 2 mg/dl Conjugated bilirubin > 2 mg/dl
Pathological Jaundice Pathological Jaundice
2 main types 2 main types
Unconjugated Hyperbilirubinemia Unconjugated Hyperbilirubinemia
Fetomaternal blood group incompatibility ( Fetomaternal blood group incompatibility (
Hemolytic Disease of the newborn) Hemolytic Disease of the newborn)
Crigler Crigler- -Najjar syndrome type I & II Najjar syndrome type I & II
Conjugated Hyperbilirubinemia Conjugated Hyperbilirubinemia
Biliary atresia Biliary atresia
Neonatal hepatitis Neonatal hepatitis
Hemolytic disease of newborn Hemolytic disease of newborn
Erythroblastosis Fetalis Erythroblastosis Fetalis
Antibody induced hemolytic disease in the Antibody induced hemolytic disease in the
newborn that is caused by blood group newborn that is caused by blood group
incompatibility between mother and fetus. incompatibility between mother and fetus.
Most common antigens Most common antigens Rh (D) and ABO Rh (D) and ABO
blood group antigens blood group antigens
Pathogenesis Pathogenesis
First Pregnancy
Second Pregnancy
Pathogenesis Pathogenesis
Fetal RBCs reach maternal circulation in last Fetal RBCs reach maternal circulation in last
trimester or during child birth trimester or during child birth
Sensitization of mother to the foreign antigens Sensitization of mother to the foreign antigens
development of antibodies that can freely development of antibodies that can freely
traverse the placenta to the fetus and cause traverse the placenta to the fetus and cause
hemolysis. hemolysis.
Hemolysis leads to progressive anemia Hemolysis leads to progressive anemia
intrauterine cardiac failure intrauterine cardiac failure Edema. Edema.
Pathology Pathology
Determined by the extent of the hemolytic Determined by the extent of the hemolytic
disease. disease.
Death in Utero Death in Utero most extreme form of disease most extreme form of disease
Hydrops Fetalis Hydrops Fetalis most severe form in live born most severe form in live born
infants. infants.
Kernicturus Kernicturus bilirubin encephalopathy bilirubin encephalopathy
Pathology Pathology Hydrops Fetalis Hydrops Fetalis
At autopsy At autopsy
hepatosplenomegaly and hepatosplenomegaly and
bile stained organs bile stained organs
Microscopically Microscopically
Erythroblastic hyperplasia Erythroblastic hyperplasia
of the bone marrow of the bone marrow
Extramedullary Extramedullary
hematopoiesis in the liver, hematopoiesis in the liver,
spleen. spleen.
Pathology Pathology Kernicturus Kernicturus
A disorder of newborns in which very high A disorder of newborns in which very high
levels of unconjugated bilirubin bind to, and levels of unconjugated bilirubin bind to, and
injure the immature neurons of the CNS injure the immature neurons of the CNS
Characterized by bile staining of the brain, Characterized by bile staining of the brain,
particularly of the basal ganglia and brain particularly of the basal ganglia and brain
stem. stem.
Diagnosis Diagnosis
Amniocentesis Amniocentesis high levels of bilirubin high levels of bilirubin
Human antiglobulin test (Coombs test) Human antiglobulin test (Coombs test)
Positive on fetal cord blood. Positive on fetal cord blood.
TREATMENT TREATMENT
Exchange transfusion Exchange transfusion
Phototherapy Phototherapy
PREVENTION PREVENTION Human anti D globulin Human anti D globulin
within 72 hours of delivery within 72 hours of delivery
Crigler Crigler- -Najjar Disease Najjar Disease
Type I Type I recessively inherited disease recessively inherited disease
Characterized by complete absence of UDP Characterized by complete absence of UDP- -
glucuronyltransferase activity. glucuronyltransferase activity.
Unremitting unconjugated Unremitting unconjugated hyperbilirubinemia hyperbilirubinemia
leading to bilirubin encephalopathy. leading to bilirubin encephalopathy.
Most patients die within first year of life Most patients die within first year of life
Crigler Crigler- -Najjar Disease Najjar Disease
Type II Type II similar to but less severe than type I. similar to but less severe than type I.
Characterized by partial decrease in the activity Characterized by partial decrease in the activity
of UDP of UDP- -glucuronyltransferase activity. glucuronyltransferase activity.
Hepatocytes have the capacity to synthesize this Hepatocytes have the capacity to synthesize this
enzyme on treatment with Phenobarbital. enzyme on treatment with Phenobarbital.
Conjugated Hyperbilirubinemias Conjugated Hyperbilirubinemias
Biliary Atresia Biliary Atresia
An idiopathic, localized, complete obliteration or An idiopathic, localized, complete obliteration or
discontinuity of hepatic or common bile ducts at discontinuity of hepatic or common bile ducts at
any points from porta hepatis to duodenum. any points from porta hepatis to duodenum.
Occurs worldwide Occurs worldwide
Most frequent cause of chronic cholestasis in Most frequent cause of chronic cholestasis in
infants and children infants and children
Most common indication for liver transplantation Most common indication for liver transplantation
in this age group. in this age group.
Clinical forms Clinical forms
Embryonic or fetal type Embryonic or fetal type 10 10- -35% 35%
early onset neonatal cholestasis early onset neonatal cholestasis
No jaundice free period after physiological jaundice No jaundice free period after physiological jaundice
No bile duct remnants in No bile duct remnants in hepatoduodenal hepatoduodenal ligaments ligaments
Associated congenital anomalies Associated congenital anomalies
Perinatal type Perinatal type 65 65- -90% 90%
Late onset neonatal cholestasis (4 Late onset neonatal cholestasis (4- -8 weeks) 8 weeks)
Jaundice free interval Jaundice free interval
Remnants of bile duct structures in Remnants of bile duct structures in hepatoduodenal hepatoduodenal
ligaments ligaments
No associated congenital anomalies No associated congenital anomalies
Prognosis Prognosis
75% survival if operated in first 60 days of life 75% survival if operated in first 60 days of life
20 20- -30% survival if operated after 90 days of life 30% survival if operated after 90 days of life
80% survival with transplantation. 80% survival with transplantation.
Idiopathic Neonatal Hepatitis Idiopathic Neonatal Hepatitis
Definition Definition
Idiopathic process Idiopathic process
Excludes known associated factors Excludes known associated factors
Alpha Alpha- -1 1 antitrypsin antitrypsin
Extrahepatic Extrahepatic biliary atresia biliary atresia
Infectious agents Infectious agents
35 35- -45% of cases of neonatal hepatitis 45% of cases of neonatal hepatitis
Male : Female Male : Female 2:1 2:1
Pathology Pathology
Giant cell Giant cell
transformation. transformation.
Diffuse, prominent Diffuse, prominent
Balloning Balloning
Acidophilic degeneration Acidophilic degeneration
cholestasis cholestasis
Clinical Features Clinical Features
Jaundice Jaundice
Dark urine Dark urine
Hepatomegaly Hepatomegaly
Prognosis Prognosis
75 75- -90 % survival 90 % survival
SIDS SIDS
Definition Definition
The sudden death of an infant under one year of The sudden death of an infant under one year of
age which remains unexplained after a thorough age which remains unexplained after a thorough
case investigation which includes: case investigation which includes:
Performance of a complete autopsy. Performance of a complete autopsy.
Examination of the death scene. Examination of the death scene.
A thorough review of the clinical history. A thorough review of the clinical history.
SIDS SIDS
Risk Factors Risk Factors
75% of SIDS deaths have no risk factors 75% of SIDS deaths have no risk factors
associated with them. associated with them.
Risk factors include: Risk factors include:
Maternal Maternal
smoking during pregnancy. smoking during pregnancy.
use of illicit drugs during pregnancy use of illicit drugs during pregnancy
Infant Infant
Prone sleeping. Prone sleeping.
Prematurity. Prematurity.
Pathogenesis Pathogenesis
Remains elusive and controversial Remains elusive and controversial
Most popular hypothesis relates SIDS to a Most popular hypothesis relates SIDS to a
Prolonged spell of apnea, followed by cardiac Prolonged spell of apnea, followed by cardiac
arrhythmia, in a susceptible, sleeping infant. arrhythmia, in a susceptible, sleeping infant.
Pathology Pathology
Gliosis of brain stem Gliosis of brain stem chronic hypoxia chronic hypoxia
medial hypertrophy of small pulmonary arteries medial hypertrophy of small pulmonary arteries
Right ventricular hypertrophy Right ventricular hypertrophy
Petechiae on the surface of lungs, pleura, heart Petechiae on the surface of lungs, pleura, heart
and thymus and thymus
SIDS SIDS
Differential Diagnosis Differential Diagnosis
Sudden explained deaths. Sudden explained deaths.
Abuse and neglect. Abuse and neglect.
Perinatal and Intrauterine Infections Perinatal and Intrauterine Infections
Ascending from the vagina and cervix. Ascending from the vagina and cervix.
Hematogenous Hematogenous dissemination from the dissemination from the
placenta. placenta.
Direct contact at birth. Direct contact at birth.
From the environment post From the environment post- -partum. partum.
Accidental introduction at the time of Accidental introduction at the time of
procedures. procedures.
Perinatal and Intrauterine Infections Perinatal and Intrauterine Infections
Perinatal and Intrauterine Infections: Perinatal and Intrauterine Infections:
Importance Importance
Perinatal and intrauterine infections are a major Perinatal and intrauterine infections are a major
cause of cause of
Intrauterine death. Intrauterine death.
Intrauterine Intrauterine embryopathies embryopathies. .
Premature labor and birth. Premature labor and birth.
Premature rupture of membranes (= PROM). Premature rupture of membranes (= PROM).
Perinatal sepsis. Perinatal sepsis.
Other perinatal problems Other perinatal problems
Protective Mechanisms for The Protective Mechanisms for The
Fetus Fetus
In In utero utero, the fetus is protected by: , the fetus is protected by:
Physical barrier of the cervical mucus plug. Physical barrier of the cervical mucus plug.
Physical barriers of the placental membranes Physical barriers of the placental membranes
and placental and placental villi villi. .
Bacteriostatic Bacteriostatic nature of amniotic fluid. nature of amniotic fluid.
Maternal immune system. Maternal immune system.
Transfer of maternal Transfer of maternal IgG IgG across the placenta. across the placenta.
Ascending Infection Ascending Infection
Extremely common Extremely common Minimal degrees of Minimal degrees of
inflammation are often seen in term placentas. inflammation are often seen in term placentas.
Although membrane rupture facilitates infection, Although membrane rupture facilitates infection,
often occurs with intact membranes. often occurs with intact membranes.
Ascending infection accounts for Ascending infection accounts for > >40% of 40% of
preterm delivery due to: preterm delivery due to:
Premature rupture of membranes. Premature rupture of membranes.
Preterm labor. Preterm labor.
Ascending Infection Ascending Infection
Most bacterial and a few viral infections ( e.g. Herpes Most bacterial and a few viral infections ( e.g. Herpes
simplex ) are acquired in this manner. simplex ) are acquired in this manner.
Fetus acquires infection by Fetus acquires infection by
Inhalation of infected amniotic fluid Inhalation of infected amniotic fluid
Passage through birth canal Passage through birth canal
Fetal infections Fetal infections
Chorioamnitis Chorioamnitis
Funisitis Funisitis
Pneumonia Pneumonia
Sepsis Sepsis
Meningitis Meningitis
Infections Acquired by the Infections Acquired by the
Hematogenous Hematogenous Route Route
TORCH infections. TORCH infections.
Congenital syphilis. Congenital syphilis.
Parvovirus B19. Parvovirus B19.
Human Immunodeficiency Virus (= HIV). Human Immunodeficiency Virus (= HIV).
Other infections. Other infections.
TORCH TORCH
Definition Definition
Complex of similar signs and symptoms
produced by fetal or neonatal infection
with a variety of pathogens.
T = Toxoplasmosis. T = Toxoplasmosis.
O = Others. O = Others.
R = Rubella. R = Rubella.
C = CMV. C = CMV.
H = Herpes simplex H = Herpes simplex
TORCH Agents TORCH Agents
Transmission Transmission
Hematogenous Hematogenous through the placenta. through the placenta.
Herpes simplex infection is an exception to this Herpes simplex infection is an exception to this
as most infections are due to: as most infections are due to:
Direct contact at the time of delivery. Direct contact at the time of delivery.
Ascending infection. Ascending infection.
TORCH Infections TORCH Infections
Common Manifestations Common Manifestations
SGA infants. SGA infants.
CNS changes: CNS changes:
Hydrocephalus. Hydrocephalus.
Microcephaly Microcephaly. .
Periventricular Periventricular
calcification. calcification.
Chorioretinitis
Pneumonitis
Petechiae
Hepatomegaly with jaundice
Splenomegaly
Bony changes resembling
osteomyelitis
Chorioretinitis
TORCH Complex TORCH Complex Blueberry Muffin Babies Blueberry Muffin Babies
Infants with TORCH Infants with TORCH
infection are often infection are often
referred to as blueberry referred to as blueberry
muffin babies as they muffin babies as they
are yellow brown are yellow brown
(=jaundice) and have (=jaundice) and have
purple spots (=petechiae) purple spots (=petechiae)
Cystic Fibrosis Cystic Fibrosis
Definition Definition
An autosomal recessive systemic disorder of An autosomal recessive systemic disorder of
exocrine glands characterized by exocrine glands characterized by
Chronic pulmonary disease Chronic pulmonary disease
Deficient exocrine pancreatic function Deficient exocrine pancreatic function
Other complications of inspissated mucus in a Other complications of inspissated mucus in a
number of organs, including the small intestine, number of organs, including the small intestine,
liver and the reproductive tract. liver and the reproductive tract.
Cystic Fibrosis Cystic Fibrosis
Pathogenesis Pathogenesis
Gene on chromosome Gene on chromosome 7 7 (7q31.2) encodes for a (7q31.2) encodes for a
protein called the protein called the CF transmembrane CF transmembrane
conductance regulator (= CFTR) conductance regulator (= CFTR). .
Phosphorylation of CFTR by protein kinase A Phosphorylation of CFTR by protein kinase A
using cAMP controls the chloride channel in the using cAMP controls the chloride channel in the
apical membranes of eccrine glands. apical membranes of eccrine glands.
cAMP is elevated by activation of adenyl cyclase cAMP is elevated by activation of adenyl cyclase
due to the binding of an appropriate chemical to due to the binding of an appropriate chemical to
a surface receptor of an epithelial cell. a surface receptor of an epithelial cell.
Cystic Fibrosis Cystic Fibrosis
Pathogenesis Pathogenesis (cont) (cont)
With the absence of CFTR: With the absence of CFTR:
In the sweat gland: increased chloride and In the sweat gland: increased chloride and
sodium concentration in sweat. sodium concentration in sweat.
In the airway: In the airway:
Stimulated chloride secretion to the gland lumen Stimulated chloride secretion to the gland lumen
does not occur. does not occur.
Increased sodium and water Increased sodium and water reabsorption reabsorption leads to leads to
dehydration of the mucous layer. dehydration of the mucous layer.
Cystic Fibrosis Cystic Fibrosis
Types of Mutations Types of Mutations
In 70 % cases In 70 % cases 3 base pair deletion that results 3 base pair deletion that results
in loss of a phenylalanine residue at position in loss of a phenylalanine residue at position
508. 508.
The remaining patients exhibit multiple (more The remaining patients exhibit multiple (more
than 170 ) different mutations. than 170 ) different mutations.
Severity of the clinical symptoms vary with the Severity of the clinical symptoms vary with the
type of type of muatation muatation. .
Cystic Fibrosis Cystic Fibrosis
Pathology Pathology
Due to thick mucus secretions: Due to thick mucus secretions:
Chronic pulmonary disease with repeated Chronic pulmonary disease with repeated
infections. infections.
Decrease in exocrine pancreas function. Decrease in exocrine pancreas function.
Other complications of inspissated mucus in: Other complications of inspissated mucus in:
Small intestine Small intestine
Liver Liver
Reproductive tract Reproductive tract
Cystic Fibrosis Cystic Fibrosis
Lung Lung
Plugging of Plugging of submucosal submucosal tracheal mucous glands tracheal mucous glands
and ducts. and ducts.
Obstruction of bronchioles with mucus Obstruction of bronchioles with mucus
associated with marked hyperplasia and associated with marked hyperplasia and
hypertrophy of the mucus hypertrophy of the mucus- -secreting cells. secreting cells.
Cystic Fibrosis Cystic Fibrosis
Lung Lung (cont) (cont)
As a consequence of bronchiolar plugging, there As a consequence of bronchiolar plugging, there
is: is:
Atelectasis. Atelectasis.
Emphysema due to destruction of parenchyma. Emphysema due to destruction of parenchyma.
Infections result in: Infections result in:
Chronic bronchitis. Chronic bronchitis.
Bronchiectasis Bronchiectasis. .
Lung abscesses. Lung abscesses.
Lung Pathology in Cystic Fibrosis Lung Pathology in Cystic Fibrosis
Normal Normal CF Lung with Destruction Due CF Lung with Destruction Due
Lung Lung to Obstruction and Infection to Obstruction and Infection
CF Lung with CF Lung with Bronchiectasis Bronchiectasis and Pneumonia and Pneumonia
Cystic Fibrosis Cystic Fibrosis
Pancreas Pancreas
In this organ, there is same mucous obstruction In this organ, there is same mucous obstruction
of ducts accompanied by: of ducts accompanied by:
Secondary dilatation and cystic changes of the distal Secondary dilatation and cystic changes of the distal
ducts. ducts.
Fibrosis. Fibrosis.
Destruction of parenchyma. Destruction of parenchyma.
These effects result in chronic These effects result in chronic pancreatitis pancreatitis in in
85% of patients with CF. 85% of patients with CF.
Pancreas in Cystic Fibrosis Pancreas in Cystic Fibrosis
Normal Pancreas with Fibro Normal Pancreas with Fibrosis, sis,
Pancreas Atrophy and Fat Infiltra Pancreas Atrophy and Fat Infiltration tion
Cystic Fibrosis Cystic Fibrosis
Pathology Pathology (cont) (cont)
Liver Liver - - Focal biliary cirrhosis late Focal biliary cirrhosis late
Due to obstruction and bile duct hyperplasia. Due to obstruction and bile duct hyperplasia.
Azoospermia Azoospermia and infertility in approximately and infertility in approximately
95% of males 95% of males
Due to failure of the vas deferens and Due to failure of the vas deferens and epididymis epididymis to to
develop. develop.
Meconium Meconium ileus ileus in 15% of infants in 15% of infants
Due to impaction of Due to impaction of meconium meconium in the terminal ileum in the terminal ileum
with subsequent risk of perforation and peritonitis with subsequent risk of perforation and peritonitis
Cystic Fibrosis Cystic Fibrosis
Clinical Features Clinical Features
Discovered between age of 2 Discovered between age of 2- -12 months. 12 months.
Child presents with symptoms of Child presents with symptoms of malabsorption malabsorption
secondary to pancreatic insufficiency: secondary to pancreatic insufficiency:
Foul Foul- -smelling smelling steatorrhea steatorrhea. .
Malnutrition Malnutrition
Edema Edema
Hypoalbuminemia Hypoalbuminemia
Failure to thrive. Failure to thrive.
Cystic Fibrosis Cystic Fibrosis
Clinical Clinical (cont) (cont)
If infant or child survives long enough, there is: If infant or child survives long enough, there is:
Upper respiratory and sinus problems. Upper respiratory and sinus problems.
Pulmonary disease Pulmonary disease
Chronic cough. Chronic cough.
Obstructive pulmonary disease. Obstructive pulmonary disease.
Recurrent pulmonary infections. Recurrent pulmonary infections.
Pulmonary disease is responsible for the Pulmonary disease is responsible for the
majority of morbidity and 80 majority of morbidity and 80- -90% of the deaths 90% of the deaths
in CF. in CF.
Cystic Fibrosis Cystic Fibrosis
Diagnosis Diagnosis
Pilocarpine Pilocarpine sweat test. sweat test.
Genetic diagnosis Genetic diagnosis
Cystic Fibrosis Cystic Fibrosis
Pilocarpine Pilocarpine Sweat Test Sweat Test
As a result of the failure to secrete chloride into As a result of the failure to secrete chloride into
the lumen of the sweat gland, there is excessive the lumen of the sweat gland, there is excessive
chloride inside the sweat gland cells. chloride inside the sweat gland cells.
Pilocarpine Pilocarpine causes secretion of the sweat from causes secretion of the sweat from
these cells: these cells:
Normal sweat: chloride = 10 Normal sweat: chloride = 10 mEq mEq/L. /L.
CF sweat, severe variant: chloride >60 CF sweat, severe variant: chloride >60 mEq mEq/L. /L.
CF sweat, mild variant: chloride = 40 CF sweat, mild variant: chloride = 40- -60 60 mEq mEq/L /L
Features of Cystic Fibrosis Features of Cystic Fibrosis
Summary Summary
Phenylketonuria Phenylketonuria
Autosomal recessive disorder characterized by Autosomal recessive disorder characterized by
Progressive mental retardation caused by a Progressive mental retardation caused by a
deficiency of the hepatic enzyme phenylalanine deficiency of the hepatic enzyme phenylalanine
hydroxylase hydroxylase. .
Occurs with a frequency of 1/10,000 Occurs with a frequency of 1/10,000
Pathogenesis Pathogenesis
Point mutation in the PAH gene on 12q. Point mutation in the PAH gene on 12q.
Deficiency of Phenylalanine Deficiency of Phenylalanine Hydroxylase Hydroxylase (PAH) results (PAH) results
in in
Hyperphenylalaninemia Hyperphenylalaninemia
Formation of Formation of Phenylketones Phenylketones
Hyperphenylalaninemia causes irreversible brain Hyperphenylalaninemia causes irreversible brain
damage damage
Complete interference with amino acid transport system in Complete interference with amino acid transport system in
brain brain
Inhibiting the synthesis of neurotransmitters Inhibiting the synthesis of neurotransmitters
Clinical Features Clinical Features
Affected infant is normal at birth Affected infant is normal at birth
Mental retardation develops within few months Mental retardation develops within few months
Tend to have fair skin, blond hair and blue eyes. Tend to have fair skin, blond hair and blue eyes.
Mousy Mousy odour odour
Treatment Treatment
Restriction of phenylalanine in diet Restriction of phenylalanine in diet
Galactosemia
An autosomal recessive deficiency of Galactose -1-
phosphate uridyl transferase, the enzyme that
catalyzes the conversion of galactose to glucose.
As a result galactose accumulates in the liver and
other organs.
Infants fed milk rapidly develop hepatosplenomegaly,
jaundice and hypoglycemia.
Cataracts and Mental retardation.
Galactosemia
M/E M/E extensive and uniform fat accumulation extensive and uniform fat accumulation
in liver in liver and marked bile ductal proliferation,
cholestasis and fibrosis.
Cirrhosis may develop in just a few months.
Galactose-free diet reverses many of the
morphologic changes.
PEDIATRIC NEOPLASMS
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Incidence. Incidence.
Tumor type. Tumor type.
Prognosis. Prognosis.
Special predispositions. Special predispositions.
Special considerations Special considerations
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Incidence Incidence
The magnitude of pediatric malignancy is much The magnitude of pediatric malignancy is much
lower than it is in adults: lower than it is in adults:
Annual mortality Annual mortality - - Adults 477,000 Children Adults 477,000 Children
1,700 1,700
On the other hand, it is the primary care On the other hand, it is the primary care
physician who has the responsibility for physician who has the responsibility for
maintaining a high index of suspicion for maintaining a high index of suspicion for
this class of disease. this class of disease.
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Tumor Type Tumor Type
Most adult malignancies are carcinomas, Most adult malignancies are carcinomas, ie ie
epithelial epithelial- -derived neoplasms. derived neoplasms.
A large number of pediatric tumors are A large number of pediatric tumors are
embryonal embryonal, , ie ie the tumor appearance seems to the tumor appearance seems to
recapitulate embryological development. recapitulate embryological development.
Tumors in the more common adult locations, Tumors in the more common adult locations, ie ie
lung, breast, prostate, and bladder, are rare in the lung, breast, prostate, and bladder, are rare in the
pediatric population. pediatric population.
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Prognosis Prognosis
Pediatric cancers are generally more responsive Pediatric cancers are generally more responsive
to therapy than are adult cancers. to therapy than are adult cancers.
Overall survival rate is approximately 60% Overall survival rate is approximately 60%
Reasons for this better prognosis are: Reasons for this better prognosis are:
Difference in tumor type between children and Difference in tumor type between children and
adults. adults.
?Increased ability of children to tolerate therapy. ?Increased ability of children to tolerate therapy.
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Special Predisposing Factors Special Predisposing Factors
Chromosomal and genetic syndromes. Chromosomal and genetic syndromes.
Congenital immunodeficiency syndromes. Congenital immunodeficiency syndromes.
>200 genetic syndromes are associated with an >200 genetic syndromes are associated with an
increased susceptibility to cancer. Among these are: increased susceptibility to cancer. Among these are:
Down syndrome ( Down syndrome (Trisomy Trisomy 21) 21) - - Acute leukemia. Acute leukemia.
Blooms syndrome (increased chromosomal fragility in culture) Blooms syndrome (increased chromosomal fragility in culture)
Leukemia Lymphoma Carcinoma Leukemia Lymphoma Carcinoma
Deletion 13q Deletion 13q - - Retinoblastoma. Retinoblastoma.
Wiskott Wiskott Aldrich syndrome Aldrich syndrome - - Lymphoma. Lymphoma.
Agammaglobulinemia Agammaglobulinemia - - Acute Acute lymphocytic lymphocytic leukemia (= ALL). leukemia (= ALL).
Pediatric versus Adult Cancer Pediatric versus Adult Cancer
Special Considerations Special Considerations
With the young age of the patient and the high With the young age of the patient and the high
survival rate, the effects of therapy on the future survival rate, the effects of therapy on the future
of the cancer survivor becomes important. of the cancer survivor becomes important.
Toxicity of treatment may: Toxicity of treatment may:
Have effects on future growth. Have effects on future growth.
Increase the rate of second tumors. Increase the rate of second tumors.
Interfere with fertility. Interfere with fertility.
Small, Round, Blue Cell Tumors Small, Round, Blue Cell Tumors
A name applied to many of the solid tumors of A name applied to many of the solid tumors of
childhood because of their appearance. childhood because of their appearance.
This appearance reflects the This appearance reflects the embryonal embryonal origin origin
of many of these tumors. of many of these tumors.
Small, Round, Blue Cell Tumors Small, Round, Blue Cell Tumors
Appearance Appearance
Relatively homogeneous, densely cellular Relatively homogeneous, densely cellular
appearance. appearance.
Tumor cells characterized by: Tumor cells characterized by:
Small size. Small size.
Lack of cytoplasm. Lack of cytoplasm.
Dark, round nuclei which stain dark blue on Dark, round nuclei which stain dark blue on
hematoxylin hematoxylin and eosin (= H&E) stains. and eosin (= H&E) stains.
Common Small, Round, Blue Cell Common Small, Round, Blue Cell
Tumors of Childhood Tumors of Childhood
Lymphoma Lymphoma
Medulloblastoma Medulloblastoma (CNS neoplasm) (CNS neoplasm)
Neuroblastoma Neuroblastoma
Embryonal Embryonal rhabdomyo rhabdomyo- -sarcoma (Sarcoma) sarcoma (Sarcoma)
Wilms tumor
Bone tumors
Ewings sarcoma/PNET
Small cell osteosarcoma
Why Should the Different Small, Why Should the Different Small,
Round, Blue Cell Tumors Be Round, Blue Cell Tumors Be
Distinguished from Each Other? Distinguished from Each Other?
Despite histologic similarities, therapy and prognosis Despite histologic similarities, therapy and prognosis
differ among these malignant neoplasms. differ among these malignant neoplasms.
Clinical information. Clinical information.
Immunohistochemistry Immunohistochemistry. .
Cytogenetics Cytogenetics. .
Molecular genetics Molecular genetics
Neuroblastoma Neuroblastoma
Definition Definition
A poorly differentiated tumor arising from A poorly differentiated tumor arising from
primitive neural crest cells that normally give rise primitive neural crest cells that normally give rise
to the adrenal medulla and sympathetic ganglia. to the adrenal medulla and sympathetic ganglia.
Neuroblastoma Neuroblastoma
General General
7 7- -10% of all childhood malignancies. 10% of all childhood malignancies.
Most common congenital tumor. Most common congenital tumor.
One of the most common solid malignant One of the most common solid malignant
tumors in children. tumors in children.
Most occur before 5 years of age. Most occur before 5 years of age.
Neuroblastoma Neuroblastoma
Clinical Features Clinical Features
Clinical manifestations depend upon the site of Clinical manifestations depend upon the site of
primary disease and extent of disease: primary disease and extent of disease:
2/3 originate in abdomen with most located in 2/3 originate in abdomen with most located in
adrenal medulla. adrenal medulla.
20% arise along sympathetic ganglia within the 20% arise along sympathetic ganglia within the
posterior posterior mediastinum mediastinum. .
In a small percentage, the primary site is never In a small percentage, the primary site is never
identified. identified.
Neuroblastoma Neuroblastoma
Presentation Presentation
Mass in abdomen, Mass in abdomen, mediastinum mediastinum, or other sites. , or other sites.
Systemic illness. Systemic illness.
Signs of Signs of metastatic metastatic disease. disease.
Neuroblastoma Neuroblastoma
Gross Pathology Gross Pathology
In adrenal medulla most In adrenal medulla most
often. often.
Lobulated Lobulated, soft surface. , soft surface.
Cut surface is reddish Cut surface is reddish- -gray. gray.
With increasing size, areas of: With increasing size, areas of:
Necrosis. Necrosis.
Hemorrhage. Hemorrhage.
Cyst formation. Cyst formation.
Gross calcification in 40 Gross calcification in 40- -
50%. 50%.
Neuroblastoma Neuroblastoma
Microscopic Pathology Microscopic Pathology
Small, round, blue cell tumor with sheets of Small, round, blue cell tumor with sheets of
undifferentiated cells undifferentiated cells + +: :
Evidence of neural differentiation. Evidence of neural differentiation.
Neurofibrillary Neurofibrillary stroma stroma. .
Pseudorosettes Pseudorosettes (= Homer (= Homer- -Wright pseudo Wright pseudo- - rosettes). rosettes).
Neurosecretory Neurosecretory granules on electron granules on electron
microscopy. microscopy.
+ for neuron + for neuron- -specific specific enolase enolase on on immunohisto immunohisto- -
chemistry. chemistry.
Neuroblastoma Neuroblastoma
Metastases Metastases
Characteristically, these tumors metastasize early Characteristically, these tumors metastasize early
with with
spread to: spread to:
Bone. Bone.
Lymph nodes. Lymph nodes.
Liver. Liver.
Bone marrow. Bone marrow.
Subcutaneous tissue. Subcutaneous tissue.
Neuroblastoma Neuroblastoma
Diagnosis Diagnosis
Elevation of urine Elevation of urine catecholamines catecholamines and and
metabolites in >90% of patients metabolites in >90% of patients
X X ray abdomen ray abdomen calcification in tumor can be calcification in tumor can be
picked up picked up
Neuroblastoma Neuroblastoma
Course Course
Neuroblastoma Neuroblastoma can take two courses: can take two courses:
Widespread dissemination in majority. Widespread dissemination in majority.
Spontaneous regression in 3 Spontaneous regression in 3- -7% due to: 7% due to:
Necrosis. Necrosis.
Spontaneous or therapy Spontaneous or therapy- -induced differentiation. induced differentiation.
Can differentiate to a benign Can differentiate to a benign ganglioneuroma ganglioneuroma
Neuroblastoma Neuroblastoma
Survival Survival
There are a number of prognostic factors which There are a number of prognostic factors which
determine survival. determine survival.
Stage Stage
Age of the patient Age of the patient
Deletion 1p Deletion 1p
N N- -myc myc amplification amplification
Overall survival is approximately 56%. Overall survival is approximately 56%.
Nephroblastoma Nephroblastoma
Definition Definition
A malignant A malignant embryonal embryonal neoplasm derived from neoplasm derived from
nephrogenic nephrogenic blastemal blastemal cells that both: cells that both:
Replicates the histology of developing kidneys. Replicates the histology of developing kidneys.
Often shows divergent patterns of Often shows divergent patterns of
differentiation differentiation
Nephroblastoma Nephroblastoma
Epidemiology Epidemiology
Incidence: 1:8,000 children. Incidence: 1:8,000 children.
No striking sex predilection. No striking sex predilection.
90% present before the age of 6 years. 90% present before the age of 6 years.
Mean age at presentation: 3.5 years. Mean age at presentation: 3.5 years.
Occasional verified cases in adults. Occasional verified cases in adults.
Environmental factors do not play a role in Environmental factors do not play a role in
development. development.
Nephroblastoma Nephroblastoma
Clinical Presentation Clinical Presentation
Usually comes to clinical attention due to the Usually comes to clinical attention due to the
detection of an abdominal mass by a parent detection of an abdominal mass by a parent
when bathing or clothing a child. when bathing or clothing a child.
Other common presentations: Other common presentations:
Abdominal pain. Abdominal pain.
Hematuria Hematuria. .
Hypertension. Hypertension.
Acute abdominal crisis secondary to traumatic Acute abdominal crisis secondary to traumatic
rupture. rupture.
Nephroblastoma Nephroblastoma
Macroscopic Appearance Macroscopic Appearance
Majority are Majority are unicentric unicentric: :
Solitary rounded masses Solitary rounded masses
sharply demarcated from sharply demarcated from
adjacent renal adjacent renal
parenchyma by a parenchyma by a
peritumoral peritumoral fibrous fibrous
pseudocapsule pseudocapsule. .
Uniform pale gray/tan Uniform pale gray/tan
appearance and soft appearance and soft
consistency. consistency.
Nephroblastoma Nephroblastoma
Microscopic Appearance Microscopic Appearance
Triphasic Triphasic: : Embryonal Embryonal tumor tumor recapitulates the recapitulates the
normal normal
development of the kidney. development of the kidney.
Blastema Blastema. .
Stroma Stroma (often (often myxoid myxoid). ).
Epithelium: tubules and Epithelium: tubules and glomeruli glomeruli. .
Nephroblastoma Nephroblastoma
Anaplastic Anaplastic Subtype Subtype
Characterized by: Characterized by:
Cells Cells> >3 times larger than adjacent cells of 3 times larger than adjacent cells of
similar type with nuclei having increased similar type with nuclei having increased
chromatin content. chromatin content.
Enlarged, bizarre, Enlarged, bizarre, multipolar multipolar mitoses. mitoses.
Nephroblastoma Nephroblastoma
Tumor Spread and Metastasis Tumor Spread and Metastasis
Restricted pattern of metastasis: Restricted pattern of metastasis:
3Ls: 3Ls:
Regional lymph nodes. Regional lymph nodes.
Lungs. Lungs.
Liver. Liver.
Metastatic Metastatic sites other than these three sites are sites other than these three sites are
unusual and should suggest other diagnoses unusual and should suggest other diagnoses
Prognosis Prognosis
Generally good Generally good
2 year survival = 90% 2 year survival = 90%
Retinoblastoma Retinoblastoma
Most common intraocular malignant neoplasm Most common intraocular malignant neoplasm
of childhood. of childhood.
Arises from retina. Arises from retina.
Retinoblastoma Retinoblastoma
Presentation Presentation
Frequently presents within first two years of life. Frequently presents within first two years of life.
Presenting signs: Presenting signs:
White pupil (= White pupil (= leukocoria leukocoria). ).
Squint (= strabismus). Squint (= strabismus).
Poor vision. Poor vision.
Spontaneous Spontaneous hyphema hyphema (= hemorrhage into the (= hemorrhage into the
anterior portion of the eye). anterior portion of the eye).
Red, painful eye. Red, painful eye.
Retinoblastoma Retinoblastoma
Gross Pathology Gross Pathology
Retinoblastoma Retinoblastoma
Microscopic Pathology Microscopic Pathology
Composed of small round cells with large Composed of small round cells with large
hyperchromatic nuclei and scant cytoplasm. hyperchromatic nuclei and scant cytoplasm.
Flexner Flexner- -Wintersteiner rosettes Wintersteiner rosettes
Retinoblastoma Retinoblastoma
Course Course
Extension into optic nerve with intracranial Extension into optic nerve with intracranial
spread. spread.
Invasion of blood vessels, especially in the Invasion of blood vessels, especially in the
highly vascular highly vascular choroid choroid, with subsequent , with subsequent
hematogeneous hematogeneous metastases. metastases.
Frequent complication is secondary glaucoma Frequent complication is secondary glaucoma
Retinoblastoma Retinoblastoma
Prognosis Prognosis
Always fatal if untreated. Always fatal if untreated.
90% survival with early diagnosis and modern 90% survival with early diagnosis and modern
therapy. therapy.
In inherited In inherited retinoblastomas retinoblastomas, patients have an , patients have an
increased susceptibility to other malignant increased susceptibility to other malignant
tumors: tumors:
Osteogenic Osteogenic sarcoma. sarcoma.
Ewing sarcoma/PNET. Ewing sarcoma/PNET.
Pinealoblastoma Pinealoblastoma. .