Pediatric pathology Flashcards
Ages of Embryo, Fetus, Neonatal, Parinatal, Infancy, Childhood
Embryo – implantation until completion of first 8 weeks
Fetus – 9 weeks to birth (legal definitions vary by state in the U.S.)
Neonatal – first 4 weeks after birth (Most hazardous)
Perinatal – 5 months before to one month after birth
Infancy – first year after birth
Childhood – between birth and puberty or legal adult age
Infant mortality rates US, Japan, Afghanistan
6.17/ 1,000 US
Japan- 2.13
Afghanistan: 117.23
In the US, infant mortality rates per 1,000 live births – black ethnicity
12.40
Most common causes of death for less than 1 year
Congenital malformations, deformations, and chromosomal anomalies
Disorders related to short gestation and low birth weight
Sudden infant death syndrome (SIDS): MOST COMMOM CAUSE >1-
most common reasons for death 1-4 years old
Accidents (unintentional injuries)
Congenital malformations, deformations, and chromosomal abnormalities
Malignant neoplasms
most common causes of death for 5-9 years
accidents
malignant neoplasms
most common causes of death for 10-15 years
accidents
Notes on congenital anomalies
present at birth
disease may not be expressed until later in life
Up to 3% of newborns have a major anomaly
The most severe anomalies cause intrauterine death (blighted ovum or abortion)
Most common birth defect
bicuspid aortic valve - 46.0/ 10,000 live births
holoprosencephaly
the cyclops one
amniotic band
- a disruption
wraps around some part of the fetus and can cut off supply to that limb/ finger/ etc.
deformations
Extrinsic disturbance of development from abnormal biomechanical forces leading to structural abnormalities
Disruptions
Secondary destruction of previously normal structure (extrinsic disturbance of normal morphogenesis)
e.g. amniotic bands, environmental causes
Not heritable!
Sequence
a pattern of cascade anomalies set off by one initiating aberration
May be called a “complex”
Malformation Syndrome
cannot be explained by a single initiating event
May be called a “complex”
Oligohydramnios (Potter) Sequence
baby not making enough urine (some osbtruction or something– Potter described it as renal agenesis)
- -> oligohydramnios
- -> pulmonary hypoplasia, altered facies, positioning defects of feet, hands, breech presentation
Potter facies: Ocular hypertelorism Low-set ears Receding chin Flattening of the nose
cleft lip/ palate
With malformation syndrome: severe cardiac defects
Can also be isolated and not part of a syndrome
Infectious Torch Syndrome
Toxoplasma Other (T. pallidum) Rubella Cytomegalovirus Herpes simplex
–> choriortinitis, cataract, conjunctivitis, microcephaly, focal cerebral calcification, microphthalmia, pneumonitis, heart disease, hepatomegaly and jaundice, splenomegaly, petechiae and purpura
atresia
absence of an opening usually in hollow organ, e.g. trachea, intestines
aplasia
Complete absence of an organ due to primordium development failure (but primordium is/was present, e.g. streak gonads)
Dysplasia of Abdominal Wall
oomphalocele- abdominal musculature fails to form (perittoneal sac is intact)
gastroschisis- part of the abdominal wall fails to form
most common congenital anomalies in huans
multifactorial and unknown
Pathogenesis of
Congenital Anomalies
Timing: Major impact on occurrence and type (4-5 weeks big impact on lots of systems including heart, CNS, eyes, etc.)
Teratogens may act in similar manner as genetic mutations
Genes affected: certain genes now known to be major players in organogenesis
Environmental Teratogens That Cause Malformations (Disruptions)*
Timing of exposure critical
Less than 3 weeks, injury lethal or induces spontaneous abortion
Between 3 & 9 weeks, very susceptible to teratogenesis with peak at 4 - 5 weeks (most organs forming)
eg. Ventricular septal defect of heart exposure
Viral infections and pregnancy
Most known: rubella and CMV
Rubella: Conception 16 weeks (50% 1st month, 20% 2nd,7% 3rd)
CMV (most common): 2nd trimester.
Rubella=rubella embryopathy: tetrad of cataracts, deafness, (numerous) heart defects, and mental retardation
CMV: CNS involvement major feature
Present with microcephaly, mental retardation, deafness, and hepatosplenomegaly
Organogenesis almost complete in second semester so frequency of anomalies lower than rubella, but damage can cause severe defects
teratogenic Drugs and Chemicals in pregnancy
13-cis-retinoic acid (=Accutane=isotretinoin) Thalidomide valproic acid (antiepileptic) disrupts HOX genes Fetal alcohol syndrome
Fetal Alcohol Syndrome
most common cause of mental retardation
growth retardation, microcephaly, atrial septal defect (ASD), short palpebral fissures, maxillary hypoplasia (affects retinoic acid and Hedgehog signaling pathways)
KEY: indistinct philthrum and wide-set eyes
Phthalates
Plasticizers added to polyvinyl chloride (PVC) and used in flexible plastics
“Exposure to in laboratory animals causes endocrine disruption and a testicular dysgenesis syndrome
Different from Bisphenol A (BPA) used in polycarbonate plastics
Maternal Diabetes
–> diabetic embryopathy
–> fetal macrosomia
caput succadaneum
(scalp edema) extremely common
cephalhematoma
common, does not cross suture lines. Check for intracranial hemorrhages
intracranial hemorrhages
major concern
Genetic Causes of Malformations
Genes producing transcription factors for embryonic/fetal development
Karyotypic (chromosomal) aberrations
Single gene mutations-e.g. holoprosencephaly/sonic hedgehog gene
Multifactorial-2 or more genes; gene(s) + environmental factor(s)
major genes controlling organ development
HOX genes, tell stuff where to go. Head: 1-4, distal 9-14
