BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/25/2013, 2nd hour
Page1
Pediatric Diseases and Genetic Screening Techniques (cont.)
Fetal Hydrops
 Term used for generalized edema of the fetus
Cystic hygroma
 Term used to describe a more localized edema in the neck area that is compatible with life.
Number of causes that can lead to generalized edema in fetus (fetal hydrops)
 Cardiovascular
 Chromosomal
 Thoracic
 Fetal anemia
 Twin gestation
 Infection
o toxoplasmosis
2 types of fetal hydrops:
 Immune hydrops
 Non-immune hydrops
Immune Hydrops
 Immune form primarily forms from the hemolytic disease of the newborn (HDN)
 Caused by blood group incompatibility between the mother and fetus: Typically Rh- mother with
a Rh+ fetus
 The mother produces antibodies against the Rh antigen
Pathogenesis
 We have a previously sensitized mother: Mother was exposed to the Rh from the first child, but
the first child escaped any issues because the mother produced IgM during the initial response,
and IgM cannot cross the placenta.
 The second child, if Rh+, will trigger the secondary immune response. IgG is primarily produced.
IgG can cross the placenta and attack the fetal red blood cells.
 We will end up with a number of issues: anemia, elevated extramedullary hematopoiesis in
secondary sites, cardiac decompensation (bc we are lysing RBCs, oxygen isn’t efficiently
delivered to the tissues, the heart will overcompensate and result in elevated pressures, this
pushes fluid out of the blood vessels and we end up with hydrops)
 Jaundice: Also arising from anemia (or breakdown of RBCs), we get hemoglobin degradation.
When hemoglobin degrades, it is converted into excessive bilirubin. That excessive bilirubin is
going to deposit in tissues throughout the fetus.
 Kernicterus: Deposition of bilirubin in the brain. Because the fetus has an underdeveloped blood
brain barrier, the bilirubin can cross the blood brain barrier and deposit in the brain (signified by
yellowing regions). This can affect neural transmission.
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/25/2013, 2nd hour
Page2
Non-immune Hydrops
 Non-immune form does not develop from an immune system incompatibility between the
mother and fetus.
 3 major causes of non-immune hydrops:
o Cardiovascular issues
o Chromosomal anomalies
o Fetal anemia
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Cardiovascular defects
o Structural or functional defects in the heart can result in intrauterine cardiac failure and
hydrops
Chromosomal Anomalies
o Turner syndrome, Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18) all
have some degree of fetal hydrops associated with them.
Fetal Anemia
o Same things happen that we saw with immune form—because of effects of anemia.
These are due to causes other than Rh or ABO incompatibilities and result in fetal
hydrops.
Fetal Hydrops Diagnosis and Treatment
 Early recognition of fetal hydrops is imperative: while fetus is still in utero.
o Good sign of potential fetal hydrops: Rising Rh antibody in the mother
o Good sign fetus has anemia: High levels of bilirubin present in amniotic fluid
 Postnatal treatment uses phototherapy—visible light can penetrate through thin skin of infant.
Light can convert the bilirubin into a compound that is readily excretable in the urine or feces so
it doesn’t deposit in the skin or brain (reduces jaundice and kernicterus). If it is a severe case,
then we will have to do a total exchange of the blood in the infant to get rid of the bilirubin. ]
Inborn Errors of Metabolism
 Detected early on after birth
 There is some sort of enzymatic defect that causes metabolic issues.
 Autosomal recessive or X-linked diseases
 Very rare
 Recessive form typically affects enzymes. Even if you have one normal copy of an enzyme, it will
be enough to carry out of full function. You have to knock out both copies in order to see full
magnitude of disease.
 Affect all of the organ systems
 Phenylketonuria (PKU)
o Autosomal recessive
o enzyme affected: Phenylalanine hydroxylase
o Child has elevated levels of phenylalanine.
o Normally, phenylalanine is converted into tyrosine with the help of phenylalanine
hydroxylase. Since the child cannot do this, it impairs brain development.
o Elevated phenylalanine inhibits neural development.
o It is very important to detect this early on so normal brain development can occur.
Typically, restriction of phenylalanine in the diet is given early in life so brain can
develop normally without that inhibition present.
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/25/2013, 2nd hour
Page3
Sudden Infant Death Syndrome (SIDS)
 SIDS is a disease of exclusion because there is no explanation for the infant’s death. It happens
suddenly and unexpectedly.
 Typically, it happens while the child is asleep, which is why it is referred to as “crib death”.
o Most of these deaths occur between the ages of 2-4 months of age.
 There are a number of potential causes:
o Parental factors
 Early maternal age (less than 20 years of age)
 Maternal smoking during pregnancy
 Drug abuse in either parent
o Infant related issues
 There could be some delayed development in the arousal and cardiorespiratory
regions in the brain, particularly the arcuate nucleus in the brainstem.
 The arcuate nucleus plays a major role in the arousal response to noxious
stimuli and thermal stress (elevated body temperature) during sleep.
 In SIDS, there could be potential that this region is underdeveloped so the child
has no response to these noxious stimuli and elevated body temperatures.
 Regions in the brainstem regulate breathing, heart rate, and body temperature.
With SIDS, this could lead to overheating, increased carbon dioxide (child cannot
expel CO2)
 SIDS in a prior sibling is associated with a 5X chance of recurrence.
o Environmental Factor that plays into the brainstem factor
 Many times, the child is found in the prone position (face down), it is expiring—
more of a CO2 enriched air. So the infant is constantly breathing in that excess
CO2. If that was any of us, something would trigger our brainstem to get us out
of that position. The child isn’t able to respond in the same way, so it
continuously brings in excess CO2.
 If the child is covered with a blanket, the warm temperatures will result in the
baby kicking off the blanket to maintain body temperature. An infant with SIDS
would not be able to detect the warm temperatures under the blanket. This
results in increasing body temperatures until issues arise.
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SIDS is not the only cause of sudden unexpected deaths in infancy.
It is a diagnosis of exclusion in which other causes are ruled out and the exact cause of death
cannot be explained.
**Infections are the most common cause of sudden unexpected death infants worldwide.
Benign Tumors of Infancy and Childhood
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3 most common benign tumors of infancy and early childhood are:
o 1) Hemangiomas (proliferating blood vessels)
 Most common tumors of infancy
 Located mainly on the skin, particularly on the face and scalp
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
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Date: 4/25/2013, 2nd hour
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 Produce flat or elevated, irregular, red-blue masses (“port wine stains”)
 Spontaneously regress in most cases (resolve on their own eventually)
2) Lymphangiomas (proliferating lymph vessels)
 Lymphatic counterpart of hemangiomas
 Characterized by cystic and cavernous spaces lined by endothelial cells and
surrounded by lymphoid aggregates
 Form lymph fluid-filled cavities
3)Sacrococcygeal Teratomas (stem from germ line of tissues)
 The most common germ cell tumor (40%+ of all cases)
 75% of these tumors are benign
 12% of the tumors are malignant and lethal
 The remaining % are immature
Malignant Tumors of Infancy and Childhood
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3 organ systems most commonly involved by malignant neoplasms in infancy and childhood are:
o 1) hematopoietic (blood ) system (this is the main one affected of the 3)
 Ex/ leukemia
o 2) neural tissue
 Ex/ retinoblastoma, neuroblastoma, any central nervous system tumors
o 3) soft tissues
 Ex/ soft tissue sarcoma (especially rhabdomyosarcoma)
Differ biologically and histologically from those in adults in the following ways:
o There is a prevalence of underlying familial or genetic aberrations/abnormalities
o Tendency of fetal/neonatal malignancies to regress (resolve) spontaneously or to
cytodifferentiate (turn into specialized cells)
 Adult tissues are already fully differentiated
o There is a high chance of survival/cure rate for many childhood tumors
o Histologically, pediatric neoplasms tend to have more embyronal microscopic
appearance and exhibit features of organogenesis
 These are called blastomas- cancer involving proliferation of cells that are not
fully differentiated (precursor cells)
Neuroblastoma
o Most common solid malignant tumor of childhood other than central nervous system
neoplasms
o Accounts for 15% of all childhood cancer deaths
o 80-90% are found in children <5 years old
o Many of these spontaneously regress and show spontaneous or therapy-induced
maturation
o Can be found anywhere in the sympathetic nervous system from head to pelvis
 75% arise in abdomen and ½ of these are found in the adrenal gland (the
adrenal medulla specifically)
 Is of neural crest origin
o Range from microscopic nodules to giant masses
Retinoblastoma
o Most common malignant eye tumor
o Mainly occurs as a congenital (from birth) tumor of neuroepithelial origin in the
posterior retina
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
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Date: 4/25/2013, 2nd hour
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If left untreated, this tumor is fatal, but if treated early on, will be extremely survivable
Diagnosis of Genetic Diseases
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Prenatal (before birth) chromosome analysis checks for potential chromosome disorders and is
performed on cells obtained by amniocentesis, chorionic villus biopsy, or umbilical cord blood
Postnatal (after birth) chromosome analysis is performed on peripheral blood lymphocytes
The examination can involve:
o Entire chromosome
 Most common type of analysis and uses karyotype (see lecture #8)
o Specific chromosomal regions
 Flourescence in Situ Hybridization (FISH)
o Specific DNA Sequences (a specific gene)
 Molecular analysis (direct and indirect gene diagnosis)
FISH utilizes DNA probes for specific chromosomal regions
o The probes are labeled with a fluorescent dye which is applied to a metaphase spread or
interphase nuclei
 The labeled chromosome(s) can be seen under microscope
 Can detect an extra chromosome (trisomy 21/ down syndrome) or a
lacking chromosome
o Allows for rapid diagnosis
Direct Gene Diagnosis
o Requires that the gene be already sequenced and cloned
o One technique relies on the fact that some mutations alter or destroy certain restriction
enzyme sites on the normal gene
 Mutations are detected by amplification of the DNA sample by PCR and
digestion of the DNA with restriction enzymes to produce fragments followed by
Southern blot hybridization analysis
o Another technique deals with mutations that affect the length of the gene
 Is also detected by PCR followed by Southern blot hybridization analysis
 Ex/ The multiple CGG repeats in Fragile X Syndrome lengthen the gene and can
be detected this way
Indications for Genetic Analysis
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Prenatal (before birth) Analysis
o When a mother has a baby and is >34 years old (increased risk of trisomy with
advancing age)
o When either parent has a previous child with a chromosomal abnormality
o When either parent is a carrier for an X-linked genetic disorder
Postnatal (after birth) Analysis
o If there are multiple congenital anomalies
o If there is unexplained mental retardation and/or developmental delay
o If there is suspected aneuploidy (abnormal chromosome number)
o If there is suspected sex chromosome abnormality
o If there is suspected Fragile X Syndrome
o If there is infertility
BHS 116.3 –Physiology III
Notetaker: Shruti Patel
Date: 4/25/2013, 2nd hour
Page6
Clicker Q
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Which is primarily a malignant tumor?
o Sacrococcygeal teratoma, hemangioma, neuroblastoma, lymphangioma