BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
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Date:04/25/2013, 1st hour
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AIMS
o Pediatric Diseases and Genetic screening techniques
Clicker Question
o Which of the following grades would you apply to a benign tumor?
 I
 II
 III
 IV
 ANSWER: I
Many of the diseases in very early childhood, <1 year of age, account for a large number of morbidity
and mortality can have more serious effects on a newborn
o Can be congenital anomalies (baby is born with), short gestation i.e. prematurity, low
birthrate and SIDS
 Most common causes of death in early childhood
o more common causes after the first year are more accident related as opposed to health
related
 Deaths related to health issues usually occurs at age or younger
 Accidents are prevalent causes of death after 1st year of age
Congenital anomalies
o Present at birth
 Doesn’t necessarily imply its heredity
 i.e. viral infection present at birth, not passed along through genes
o Usually have errors in morphogenesis i.e. development of fetus 5 primary types
 Malformation
 Intrinsic errors—defect in fetus causing malformation
 Multifactorial causes some underlying defect from the fetus that is
compounded by some other effect like gene defect + chromosomal defect or
gene defect and environmental factor
 Usually stems from the fetus itself
 Ex. Polydactyly
o Extra digits
 Syndactyly—digits that are fused together
 Disruption
 Fetus is growing normally, but now we have an extrinsic disturbance
occurs outside the fetus
 Something that causes a rupture of the amniotic sac as an example
o Amniotic sac is a fibrous sac that is filled with fluid that fetus bathes
in
o If disrupted—have a bunch of fibrotic bands  amniotic bands
o Fluid leaks out and bands tighten up around fetus and the bands
impinge on certain regions that are developing on the fetus
o Ex. Amniotic band came across where the hand was developing
prevented the normal development of the hand
 Have fingers that are stunted
o Disruption type of defect
 Everything goes along normally—but some external factor
disrupts morphogenesis
 Deformation
 Extrinsic something outside fetus causes this problem
 Effects 2% of newborn infants to a varying degree
BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
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Date:04/25/2013, 1st hour
Page2
Some sort of generalized compression via a biomechanical force
o Most common is uterine constraint—not enough room in uterus for
fetus to grow
o Maternal causes first pregnancy; small or malformed uterus
o Fetal causesmultiple fetuses (twins, triplets, etc.) need room for
all fetuses inside the uterus, causing constraint on the others
 Sequences
 Common example= Potter sequence
 Multiple congenital anomalies arise from a single defect in organogenesis
one of the fetal organs isn’t developing properly, resulting in a cascade of
events that lead to error in morphogenesis
 With the Potter sequence we have Oligohydramnios decreased production
of amniotic fluid
o Most common trigger renal agenesis
 Kidneys are underdeveloping in the fetus
 When the fetus urinates, the kidneys eliminate fluid which
goes into amniotic sac and contributes to amniotic fluid BUT
if have underdeveloped kidneys not producing as much
fluid not as much fluid in amniotic sac—sac acts as a
cushion so if there is less of a cushion/shock absorber
fetus is more susceptible to potential deformations
 Amniotic leak also decreases the cushion
 These cause fetal compression club foot development, smashed forehead
due to loss of cushion
 Malformation syndrome
 Several defects that can’t be explained by one of the single errors in
morphogenesis usually a combination of a single factor like a viral
infection or chromosomal abnormality leading to a number of tissues being
affected by this end up with multiple deformations arising from this
Causes of congenital anomalies
o 50% are unknown (idiopathic)
o The rest are under 3 major categories
 Genetic
 Chromosomal, single gene defects
 Environmental
 Viruses, bacteria, chemical toxins
 Toxoplasmosis—found in cat feces, which is why pregnant women shouldn’t
clean the cat litter box
 Multifactorial
 Combo of genetic and environment
o Genetic causes 
 Chromosomal
 Associated with some sort of congenitial malformation
 Down syndrome, Patau syndrome result in some sort of malformation
along with the other things that they cause
 These are typically not inherited diseases chromosomal defects develop
during oogenesis or spermatogenesis
o Not carried on autosomal genes
 Single gene defect
 90% are autosomal dominant or autosomal recessive
BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
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Date:04/25/2013, 1st hour
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Many involve genes specifically responsibly for normal organogenesis and
development if defect = malformation in specific organ or limb
 Polydactyl and syndactyly are triggered by defect in a single gene gene =
sonic hedgehog
Environmental causes
 Viruses
 Drugs or chemicals that the mother takes
 Thalidomide causes a lot of deformations back in the 70s
 Alcohol can lead to fetal alcohol syndrome
 Androgens
 Retinoic acid  Accutane (used for severe acne)
 Radiation
 Maternal diabetes altered glucose can have effects on development of child
Multifactoral causes
 Genetic predisposition + environmental trigger
 Used to see a lot of neural tube defects because there was a lack of folic acid in
maternal prenatal multivitamins
 lack of folic acid leads to neural tube defects
o child needed to be genetically predisposed along with the lack of
folic acid in the diet triggered neural tube defect
 now folic acid is in prenatal vitamins, so neural tube defects aren’t
encountered as frequently
Pathogenesis of congenital anomalies
 When during fetal development are these factors presented to the fetus?
 Timing is very important
 First 8-9 weeks = embryonic period
 Sensitive time point to be exposed to any environmental insults
 1-3 weeksembryo is so small so exposure to toxins can either cause
spontaneous abortions; or will be able to recover from damage because such
an early stage of development
 Weeks 4-5 are prime organ development time frame
o Organogenesis is occurring
o Exposure to some environmental toxins/teratogens can result in
serious problems developing in organogenesis
o Very sensitive to exposure to external toxins
 Week 10-birth = fetal period
 Organs have already formed
 If there is an environmental insult may just affect the size of the organ, or
it can trigger some other things, but won’t have an effect on the development
 won’t be any major morphological alterations at this point
 The fetus can be subjected to growth retardation at this point might stunt
fetal growth, everything forms but doesn’t grow to full capacity
 Toxins/environmental insults that effect organ development = teratogens
 One of the most common ones = retinoic acid
 Fetus needs Vitamin A to develop normally
 Vitamin A taken in natural form is required and not an issue
o Mother takes Vitamin K, gets converted to retinol, retinol is taken up
by fetal tissue
BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
Date:04/25/2013, 1st hour
Page4
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in fetal tissues, retinol is converted to retinoic acid, which goes and
acts on DNA to trigger patterning genes
o if retinoic acid is converted from vitamin A in fetal cells directs
patterning properly
If mother takes retinoic acid in retinoic acid form becomes toxic
o Has opposite effect and stunt/inhibits normal organ growth resulting
in retinoic acid embryopathy
o Accutane has been shown to result in retinoic acid embryopathies
Prematurity
o Fetus born before completion of normal gestation—38-39 weeks
o Defined as gestational age of less than 37 weeks
o Most common causes
 PPROM
 Preterm premature rupture of placental membranes
 30-40$ of premature births are caused by this
 2 common risk factorsmaternal smoking and prior history of premature
birth
 Intrauterine infections
 Account for 25% of cases of premature births
o Don’t confuse premature with fetal growth restriction
 Fetus growth restriction goes through full term but growth is just restricted,
primarily due to intrauterine growth retardation
 Fully developed but organ growth is stunted
o Immaturity of organ systems in premature birth
 Organs still go through maturation processes during fetal period that require full term
in utero
 Lungs
 Alveolar development occurs later in development—can be incomplete
 Kidneys incomplete glomeruli development
 Brain involutions in the brain occur during end of fetal development, less sulci and
gyri therefore have a smoother brain instead of having involutions
 Myelination develops later
 Liver some of the functions may not have fully developed in a premature infant
 Can see jaundice present in a premature child
o Apgar score
 Doctors perform tests on newborn to give it an Apgar scoregives a method to
evaluate physiologic condition and responsiveness, gives the doctor a good idea of
the chances of survival within the first 5 minutes
 5 major parameters: Heart rate, respiratory effort, muscle tone, response to catheter in
nostril and color
 Rates each of these parameters from 0-2
 If everything was perfect = score of 10
 If things were all absent= lowest score = 0
 Measure at 1 min and 5 min after delivery
 If after 5 min, score is 0-1, the mortality rate is approximately 50% within 1st month
 If score is 4 = mortality is 20%
 Score of 7 or greater = 100% survivability within a month (0% mortality)
Perinatial infections
o Occur close to time of birth
o 2 types
BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
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
Date:04/25/2013, 1st hour
Page5
Transcervical infections (ascending infections)
 Typically going to be bacterial in nature
o Common = streptococcus
o Few viral infections can be ascending herpes simplex
 Infection that is spread in utero
 Doesn’t have to effect child while in uterus, can also happen during the
birthing process
 Child can acquire the bacteria during the process of birth via inhaling
amniotic fluid or inhale bacteria and get it in its lungs
 Usually lead to placental membrane inflammation if it does happen while its
still in utero or funisisits = inflammation of the umbilical cord
 Transplacental infections (hematologic infections)
 Blood borne – spread from blood of mother across placenta into fetus
 Primarily virus infections—can also be parasites and some bacteria
 Most common organisms = TORCH
o Toxoplasma, Other microbes, Rubella virus, Cytomegalovirus,
Herpes virus
o Cause very similar symptoms fever, encephalitis, chorioretinitis,
conjunctivitis, premature cataract, pneumonia etc.
 TORCH infection ocular issues
o Conjunctivitis, choreoretinitis, premature cataracts
 Ocular systems found in a child from one of these viruses in
a transplacental infections
 Heart defects, pneumonia and hepatitis = life threatening issues that can
occur as well
Neonatal respiratory distress
o Caused by a number of things
 Mother could have been sedated during birthing process, anesthetic could get into
fetal blood and cause respiratory issues with breathing of the fetus
 Head injury during birthing process
 Aspirating blood or amniotic fluid during birth
o Most common cause  respiratory distress syndrome i.e. hyaline membrane disease
 Disease where we get the formation of membranes in airspaces of the fetal lungs
o Pathogenesis of RDS
 Disease of prematurity—lungs have not fully developed
 Affects 15-20% of infants born between weeks of 32-36 weeks
 Increases to 60% in those born before 28 weeks
 Lungs are unable to make surfactant  alveoli are going to collapse
 Reduced surfactant synthesis, release  leads to decreased alveolar
surfactant see alveolar collapse = atelectasis
 If alveoli collapse, have nowhere for oxygen and CO2 to be exchanged with
fetal blood 
o have hypoxemia develop i.e. decreased oxygen  blueing of fingers
and such that occurs
o Excessive carbon dioxide retention in blood can’t exchange to
expire it leading to acidosis will occur
 Number of other things occurring = end formation  inflammatory
condition with fibrin deposits forming in the alveoli further blocking any
type of exchange of oxygen and CO2
BHS 116.3 Human Physiology and Pathology
Notetaker: Caitlyn McHugh
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
Date:04/25/2013, 1st hour
Page6
No surfactant produced hypoxemia and CO2 retention leads to fibrin deposits
occurring
 Infants with RDS
 Appear normal at birth
 Varies from a few minutes to hours start to develop very labored breathing
that progressively worsens
 Very important to monitor infants for a period of time after birth in order to
ensure they don’t have RDS
 Early cause of death in neonatal period
Clicker question
o Which type of perinatal infection is transmitted through the blood?
 Transcervical
 Transplacental
 ANSWER: TRANSPLACENTAL