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Documente Cultură
Discuss
the
pathogenesis
of
deformations,
and
give
examples
of
underlying
factors,
which
may
lead
to
deformations
via
such
pathogenetic
mechanisms.
a. Deformations:
Definition
localized
or
generalized
compression
of
the
growing
fetus
by
abnormal
biomechanical
forces
Will
hit
after
8
weeks.
i. Arises
later
in
development
than
malformations.
This
is
because
the
fetus
already
has
developed
various
of
the
body
(arms,
legs,
ect)
that
become
influenced
by
biomechanical
forces.
ii. The
MOST
COMMON
DEFORMATION
=
UTERINE
CONSTRAINT
1. Factors
that
affect
the
propensity
for
a
fetus
to
be
affects
by
uterine
constraint
Maternal
factors
Fetal
factors
First
pregnancy
Multiple
fetuses
Small
uterus
Oligohydramnios
Leiomyoma
Abnormal
presentation
iii. Sequence:
Potter
Sequence
1. Sequence
that
describes
the
pathogenesis
of
multiple
congenital
abnormalities
that
result
from
secondary
effects
of
a
single
localized
aberration
in
organogenesis.
2. The
INITIATING
event
may
be
malformation,
deformation,
or
disruption.
b. One
of
the
risk
factors
for
deformation
is
oligohydramnios,
and
a
well
studied
sequence
called
the
potter
sequence
describes
factors
that
result
in
oligohydramnios
and
the
affect
it
can
have
on
a
fetus.
c. oligohydramnios
-->
compression
of
fetus
-->
limb
deformities
-->
facial
anomalies/
deformities
and
pulmonary
hypoplasia
which
is
the
cause
of
death
-
this
is
all
due
to
the
lack
of
the
childs
ability
to
urinate
during
in-utero
-->
Lack
of
Pee
results
in
Potter
sequence.
The
oligohydramnios
causes
i. Fetal
compression
1. Altered
facies
2. Defects
of
limbs
3. Breech
presentation
ii. Pulmonary
hypoplasia
2. List
the
most
common
birth
injuries
(cranial
injuries,
fractures,
peripheral
nerve
injuries,
and
liver
rupture)
a. Mechanical
to
anoxic
(low
02)
damage
b. Occur
in
5/1000
live
births
c. Predisposing
factors:
cephalopelvic
disproportion
(disproportionate
child
head
is
larger
than
mothers
pelvis
http://www.youtube.com/watch?v=Pr216HObUIA),
difficult
labor
(breech
presentation
child
exits
womb
feet
first
rather
than
head
first.),
Prematurity
(neonate
is
not
able
to
handle
the
stressors
of
the
new
environment.
Depending
on
how
the
child
responds
to
this
new
environment
he/she
will
be
assigned
a
number
=
THE
APGAR
SCORE
(will
be
covered
later
in
objectives
but
a
quick
look
=
its
a
number
that
determines
the
chances
of
survival
are
by
assessing
childs
physiological
condition
and
responsiveness
3. Discuss
intrauterine
and
perinatal
infections
in
terms
of:
a. Routes
of
spread
i. Ascending
from
the
vagina
and
cervix
ii. Hematogenous
dissemination
from
the
placenta,
then
from
placenta
into
amniotic
fluid
(transplacental
infection
Consider
all
of
the
TORCHEs)
iii. Direct
contact
at
birth
iv. From
environment
post
partum
v. Accidental
introduction
at
the
time
a
procedure
ie
amniocentesis.
*First
two
are
most
common
routes
b. Common
causative
organisms
i. Ascending
infection
Mostly
d/t
bacteria,
some
by
virus
passage
through
birth
canal.
1. Clinical
pathologies:
Chlorioamnionitis,
Funisitis,
Pneumonia,
Menigitis,
Sepsis
ii. Hematogenous
spread
=
TORCH
and
SLAVE
iii. Toxoplasmosis
iv. Other
infections
slave
v. Rubella
vi. CMV
vii. HSV,
HIV
1. SLAVE
2. Syphilis
3. Listeria
monocytogenes
4. Adenovirus
5. Varicella
6. Enterovirus
4. State
the
most
common
cause
of
death
in
children,
as
well
as
the
most
common
non-traumatic
cause
of
death
in
children:
a.
under
one
year
of
age
i. congenital
abnormalities,
deformations
and
chromosomal
anomalies
ii. traumatic
maternal
complications
of
pregnancy
b.
between
one
and
four
years
of
age
i. traumatic
injuries
ii. non
traumatic
congenital
anomalies
c.
between
five
and
fourteen
years
of
age
i. traumatic
injuries
ii. non
traumatic
malignant
neoplasms
5. List
the
common
abnormalities
in
morphogenesis
and
discuss
their
etiopathogenesis.
(Malformation,
Disruption,
Deformation,
sequence)
a. Malformation
(primary
structural
abnormality)
i. Intrinsic
abnormal
developmental
process.
Primary
structural
abnormality
with
poor
formation
of
tissue
due
to
localized
error
that
occurs
DURING
development.
ii. Examples
of
malformation:
Polydactyly
and
syndactyly,
cleft
lip,
cleft
palate,
congenital
heart
disease
iii. Malformation
syndromes
The
presence
of
>1
developmental
anomalie
of
>2
systems
due
to
a
common
etiology
1. Examples:
Down
Syndrome
and
Klinefelter
interestingly
klinefelters
is
more
common
than
downs
in
males
(1:600
compared
to
1:500)
b. Disruption
(secondary
cause
of
structural
abnormality)
i. Structural
defect
caused
by
SECONDARY
DESTRUCTION
or
interface
with
a
previously
normally
formed
part.
A
disruption
arises
from
an
EXTRINSIC
disturbance
in
morphogenesis.
1. extrinsic
disturbance
in
the
morphogenesis
ii. Example:
Amniotic
band
entanglement
followed
by
amputation
or
disfigurement
of
a
formed
body
part.
(infarction,
necrosis)
1. Amniotic
band
disruption
sequence
c. Deformation
(occurs
later
in
fetal
life
due
to
compression)
i. (localized
compression
of
the
growing
fetus
by
abnormal
biomechanical
forces)
ii. Explained
in
first
objective
iii. Example:
Uterine
constraint
1. POTTER
SEQUENCE
2. Sequence
Sequence
refers
to
multiple
congenital
anomalies
that
result
from
secondary
effects
of
a
single
localized
aberration
in
organogenesis.
The
initiating
event
may
be
a
malformation,
deformation,
or
disruption.
An
excellent
example
is
the
oligohydramnios
(or
Potter)
sequence.
6. Define
Prematurity
and
intrauterine
growth
retardation
(IUGR)
discuss
common
complications
of
Prematurity
a. Prematurity
and
intrauterine
growth
retardation
is
the
second
cause
of
death
in
the
fetus.
b. Prematurity
birth
preterm,
which
is
less
than
37
weeks
or
a
weight
below
2500g.
Normal
term
infant
is
37-43
weeks.
Below
2500g
can
be
characterized
as
either
premature
or
IUGR
for
their
gestational
age
thus
would
be
classified
as
Small
Gestational
Age
(SGA
=
Below
10th
percentile
for
age).
c. Define
IUGR:
this
classification
defines
a
set
of
causes
that
result
in
abnormal
or
hindered
development
of
the
child.
Further
subclasses
are
symmetrical
IUGR
and
asymmetrical
IUGR.
Symmetrical
and
asymmetrical
refer
to
the
developmental
affects
on
the
child,
for
instance
symmetrical
IUGR
means
that
both
the
head
and
body
are
equally
affected
by
the
development
growth
abnormality,
whereas
in
asymmetric,
the
brain
gets
precedence
and
will
not
be
as
severely
affected
by
the
developmental
abnormality
as
compared
to
the
rest
of
the
body.
Major
Risk
Factors
of
Prematurity:
1.
Premature
rupture
of
membranes
2.
Intrauterine
infections
3.
Structural
abnormalities
of
the
uterus,
cervix,
or
placenta
4.
Multiple
gestations
Describe
the
complications
prematurity:
d. Hyaline
membrane
disease
(respiratory
distress
syndrome
of
the
newborn)
i. The
most
common
cause
of
infant
death
in
the
united
states
ii. Formation
of
hyaline
membranes
in
peripheral
alveoli.
Differ
from
ARDS
in
ARDS
the
onset
is
due
to
some
infection
or
drug
intake
which
results
in
hyaline
membrane
containing
PMNs,
fibrin,
platelets,
whereas
in
RDS
-
the
hyaline
membrane
will
only
contain
fibrin
and
platelets
iii. Immaturity
of
type
II
pneumocytes
results
in
decrease
surfactant
production,
decreased
compliance
iv. Causes
of
RDS:
1. Prematurity
-
#1
cause
2. Perinatal
asphyxia
3. Maternal
diabetes
-
excess
insulin
has
been
shown
to
decrease
surfactant
production
4. C-Section
-
normal
birth
through
canal
is
going
to
stimulate
adrenaline
release
which
is
going
to
stimulate
type
II
pneumocytes
to
secrete
surfactant
-
thus
with
a
C-section
-
there
is
no
vaginal
birth
and
less
adrenaline
will
be
present
within
the
child.
5. Twin
gestation
6. Male
Sex
CXR
->
Ground
glass
opacities
Timing
Less
than
12
hours
12-24
hours
Microscopy
NECROTIC
CELLULAR
DEBRIS
IN
TERMINAL
BRONCHIOLES
and
ALVEOLAR
DUCTS
HYALINE
MEMBRANES,
Membranes
are
composed
of
necrotic
alveolar
type
II
pneumocytes
and
fibrin,
remember
NO
PMNs
(thats
in
ARDSs
Hyaline
membranes)
Evidence
of
reparative
changes,
including
proliferation
of
type
II
pneumocytes
and
interstitial
fibrosis
e. Necrotizing
enterocolitis
i. Disease
or
premature
infants
along
with
infants
of
low
birth
weight
results
in
mortality
of
20-50%
ii. In
clinical
vignette
look
out
for
following
formula
feeds
and
preterm
infant
iii. Bacterial
colonization
of
the
gut
iv. Clinical
features
Abdominal
distention,
bloody
stools,
DIC,
progressing
to
death
v. Diagnosis
Abdominal
radiographs
will
show:
DILATED
LOOPS
OF
BOWEL
-
WILL
SEE
GAS
IN
LOOPS
OF
BOWEL
=
PNEUMATOSIS
INTESTINALIS
-->
NEC
will
affect
the
terminal
ileum
to
ascending
colon.
vi. MORPHOLOGY:
coagulative
necrosis
extending
into
muscularis
mucosa
1. Coagulative
necrosis
of
mucosa
breaching
through
submucosa
and
muscularis
mucosa.
Also
characteristic
air
filled
spaces
beneath
the
mucosa
-
pneumatosis
intestinalis.
vii. Complications
Early
Sepsis,
shock,
DIC,
acute
tubular
necrosis
leading
to
acute
renal
failure
and
intestinal
perforation
Late
Short
gut
syndrome,
malabsorption,
and
stricture
formation
f. Intraventricular
and
germinal
matrix
hemorrhage
i. Bleeding
into
the
germinal
matrix
with
extension
into
the
ventricles
and
beyond.
N/B
germinal
matrix
is
a
source
of
nerve
cells
in
embryo
and
fetuses
(up
to
33
wks
of
gestation)
thus
following
33wks
this
will
not
present.
Germinal
area
is
a
rich
vascular
network
thats
sensitive
to
anoxia.
4
grades.
ii. Rapid
death
can
ensue
massive
hemorrhage,
falx
cerebri
herniation,
however
if
child
survives
will
see
cavitations
or
pseudocysts
SURROUNDED
BY
HEMOSIDERIN
LADEN
MACROPHAGES
and
GLIOSIS
7. Describe
the
following
disorders:
a.
congenital
rubella
syndrome
b.
bronchopulmonary
dysplasia
(BPD)
c.
cystic
fibrosis
(CF,
mucoviscidosis)
d.
Dubin-Johnson
syndrome
e.
phenylketonuria
f.
galactosemia
g.
sudden
infant
death
syndrome
(SIDS)
Disorder
Incidence
Etiology
and
Morphology
and
Epi
Path
Congenita Frequency
Maternal
rubella
Inclusion
bodies,
lymphocytic
l
Rubella
2-3%
for
all
infection
in
FIRST
infiltrate
check
with
dani
and
Syndrome
congenital
trimester
harris
not
in
notes
not
in
robbins
abnormaliti Vertical
es
transmission
hematogenous
thru
placenta
TORCH
Bronchop
Long
term
-peribronchial
fibrosis
ulmonary
sequelae
of
-fibrotic
obliteration
of
bronchioles
dysplasia
neonatal
RDS
-OVER
DISTENDED
ALVEOLI
(BPD)
-Caused
by
-squamous
metaplasia
of
bronchial
arrested
epithelium
development
of
-increase
levels
of
TNF,
macrophage
alveolar
septation
inflammatory
protein
1,
IL-8
at
SACCULAR
stage
of
development
Cystic
Discovered
-AR
Phosphorylation
of
CFTR
by
PKA
Fibrosis
at
2
-12
-F508
ch7,
CFTR
using
cAMP
chloride
channel
in
months
-Most
common
in
apical
membrane
of
exocrine
gland
whites
resulting
in
thick
mucous
secretions.
-TWO
CLINICAL
Complications:
CUES
in
children
-Atelectasis
-NASAL
POLYPS
-Emphysema
-RECTAL
-Bronchiectasis
(Cystic
fibrosis
that
PROLAPSE
leads
to
bronchiectasis
will
be
present
in
upper
lobe
whereas
other
forms
of
bronchiectasis
due
to
infection
will
be
present
in
lower
lobes
of
lung)
-Pancreas:
Secondary
dilation
and
cystic
changes
of
distal
ducts
and
atrophy
of
secretory
cells,
FIBROSIS,
and
destruction
of
EXOCRINE
Clinical
course
PDA,
Cataracts,
deafness
=
classic
triad.
Alveolar
hypoplasia
(decrease
in
number
of
mature
alveoli)
-chronic
pulm
disease
with
repeated
infections
-def.
pancreatic
function
-inspissated
mucous
in
SI,
liver,
and
reproductive
tract
-Lung
obstruction
of
bronchioles
with
mucous.
Marked
hyperplasia
and
hypertrophy
of
Goblet
/
alveolar
parenchyma.
-Liver:
FOCAL
BILIARY
CIRRHOSIS
(late)
d/t
obstruction
and
bile
duct
hyperplasia.
AZOOSPERMIA
AND
INFERTILITY,
may
see
meconium
in
SI.
Dubin-
Johnson
-AR
-Defective
transport
of
conjugated
bilirubin
from
hepatocytes
to
canicular
lumen
Phenylket
onuria
Maternal
disease
-AR
-Pt
mutation
on
ch.12q
(long
arm)
-def.
in
phenyalanine
hydroxylase
Galactose
mia
-BLACK
LIVER
-Accumulation
of
coarse,
iron
free,
DARK
BROWN
granules
in
hepatocytes
and
Kuppfer
cells,
then
on
EM
pigment
is
located
in
lysosomes
and
composed
of
EPINEPHRINE
metabolites
NOT
BILIRUBIN
PIGMENT
-hyperphenylalaninemia
causes
irreversible
brain
damage
-formation
of
phenylketones
cells.
Presentation
-foul
smelling
steatorrhea
-malnutrition
-edema
-failure
to
thrive
Asymptomatic
except
for
mild
jaundice
-INFANT
WILL
BE
NORMAL
AT
BIRTH,
then
will
develop
mental
problems
after
few
months.
-microcephaly
-mental
retardation
-growth
retardation
-congenital
heart
defects
-MOUSY
ODOR
TO
URINE
-FAIR
SKIN,
BLUE
EYES,
BLONDE
HAIR
lack
of
melanin.
AR
Extensive
and
uniform
fat
Infants
fed
milk
-def
of
galactose- accumulation
in
the
liver
and
marked
rapidly
develop
1
phosphate
bile
duct
proliferation,
cholestasis,
hepatosplenomegaly
uridyl
transferase
and
fibrosis
,
jaundice
and
-Cirrhosis
may
develop
in
few
hypoglycemia
months
-Cataracts
and
mental
retardation
Sudden
infant
death
syndrome
-Sudden
death
of
an
infant
under
one
year
of
age
-To
make
diagnosis
investigation
includes:
-Complete
autopsy,
exam
scene
where
death
occurred,
and
review
of
clinical
history.
-Pathogenesis:
popular
hypothesis
prolonged
spell
of
apnea
followed
by
cardiac
arrhythmia
-Gross:
petechia
on
surface
of
lung,
pleura,
heart
and
thymus.
Gliosis
of
brain
stem,
-Morph:
MEDIAL
hypertrophy
of
small
pulmonary
arteries
and
extramedullary
hematopoiesis.
Childhood
cirrhosis:
-A1At
def
-Biliary
atresia
-Galactosemia
-Wilson's
disease
-Cystic
Fibrosis
8. Discuss
various
causes
of
neonatal
jaundice
a.
Hemolytic
disease
of
the
newborn
b.
Crigler-Najjar
syndrome
c.
Rotor
syndrome
d.
Biliary
atresia
e.
Idiopathic
neonatal
hepatitis
Causes
of
Etiology
and
Path
Morphology
Neonatal
Jaundice
Hemolytic
Pathological
jaundice
2
-Ab
induced
hemolytic
disease
disease
of
the
types:
unconjugated
and
that
is
caused
between
the
newborn
conjugated
HDoN
=
mother
and
fetus
due
to
unconjugated
incompatibility
of
blood
types.
hyperbilirubinemia
-Most
common
antigens
Rh
and
-Erythroblastosis
Fetalis
ABO.
Crigler
Najjar
Syndrome
Pathological
Jaundice
Normal
liver
morphology
unconjugated
hyperbilirubinemia
-AR
-Type
I
COMPLETE
absence
of
UDP-
glucoronyltransferase
unconjugated
hyperbilirubinemia
leading
to
bilirubin
encephalopathy
-Type
II
Less
sever
50%
active
UDP
gtf
enzyme
Clinical
Course
-Death
in
utero
most
extreme
form
-hydrops
fetalis
most
severe
form
in
live
born
infants
-kernicterus
bilirubin
encephalopathy
Type
I
most
patients
die
within
the
first
year
of
life.
-Jaundice,
kernicterus,
increase
in
unconjugated
bili
-Type
II
is
treatable
with
Phenobarbital
whereas
type
I
is
not.
Rotor
Syndrome
a
milder
form
of
Dubin-
Johnson
Biliary Atresia
Idiopathic
Neonatal
hepatitis
Familial
conjugated
hyperbilirubinemia
-Idiopathic
-Defect
in
the
excretion
of
conjugated
bilirubin
into
the
biliary
canaliculi
with
the
bilirubin
being
absorbed
into
the
blood
Conjugated
Hyperbilirubinemia
-complete
obstruction
of
the
lumen
of
the
extrahepatic
biliary
WITHIN
FIRST
THREE
MONTHS
OF
LIFE
-Most
frequent
cause
of
GALL
STONES
in
infants
-Most
common
INDICATION
for
liver
transplant
in
infants
-idiopathic
-50-60%
of
neonatal
hepatitis
-More
MALES
than
females
-Jaundice,
epigastric
discomfort,
episodic
pain,
fever
-Jaundice
-Dark
Urine
-Hepatomegaly
Clinical
Prognosis
Behavior
-Mets
to
bones,
lymph,
liver,
BM,
subq
tissues
Retinobl
astoma
Wilms
tumor
(nephrob
lastoma)
2-5yrs
-#1
renal
tumor
Sporadic
WT1
(WAGR
syndrome
and
Denys-Dash
syndrome)
WT2
=
Beckwith-
Weildman
Neuroblastoma
-Staging
-TrkA
=
increased
expression
indicates
good
prognosis.
-Deletion
of
1p
or
gain
of
17q
=
poor
prognosis
3Ls
-
tumor
spreads
to
lungs,
liver,
lymph
nodes
-
if
met
occurs
to
other
organs
than
the
3Ls
then
its
not
likely
to
be
wilms
Retinoblastoma:
Nephroblastoma:
DOWN
SYNDROME
EDWARD SYNDROME
PATAU SYNDROME