Robbins Flashcards
Two main classes of congenital anomalies and examples for each.
Genetic:
chromosomal aberrations: Down syndrome, Turner syndrome
Mendelian inheritance: holoprosencephaly
Environmental:
Maternal/Placental infections: TORCH
Maternal disease states: Diabetes, obesity, PKU
Drugs and chemicals: alcohol, folic acid antagonists, 13-cis-retinoic acid, phenytoin, thalidomide, warfarin
During which weeks of development is the embro/fetus most susceptible to teratogens?
Between weeks 3 - 9, embryo is extremely susceptible to teratogens.
PEAK sensitivity: weeks 4 - 5.
Define embryonic & fetal periods (in terms of weeks):
Fetal: first 9 weeks
Embryonic: 9 weeks - birth.
<37 weeks = premature
Name 4 environmental teratogens.
Alcohol
Valproic acid
Cyclopamine
Retinoic acid
What are the top two causes of neonatal mortality?
Congenital anomalies
Prematurity
What are the top 4 major risk factors for prematurity?
PPROM: premature preterm rupture of membranes.
Intrauterine infection.
Uterine, cervical and placental structural abnormalities.
Multiple gestation.
List clinical risk factors for PPROM.
Prior hx of preterm delivery. preterm labor and/or vaginal bleeding during the current pregnancy. maternal smoking. Low SES. poor maternal nutrition.
What are the histologic correlates of intrauterine infection?
Chorioamnionitis: inflammation of placental membranes.
Funisitis: inflammation of fetal umbilical cord.
What are the 4 main hazards of prematurity?
Neonatal respiratory distress syndrome (hyaline membrane disease).
Necrotizing Enterocolitis (NEC).
Sepsis.
Intraventricular and germinal matrix hemmorrhage.
Give at least one example each of maternal, fetal and placental abnormalities that lead to fetal growth restriction.
Maternal: preeclampsia; hypertension; narcotics, alcohol and smoking; chemotherapy, phenytoin; malnutrition.
Fetal: THESE ARE SYMMETRICAL; chromosomal disorders (trisomies); congenital anomalies; congenital infections (TORCH);
Placental: THESE ARE ASYMMETRICAL; vascular anomalies (single umbilical artery, abnormal cord insertion, placental abruption, placenta previa, thrombosis and infarction; chronic villitis of unknown etiology; multiple gestations.
List 5 causes of respiratory distress in the newborn
RDS (pulmonary immaturity, deficiency of surfactant –> hyaline membrane disease)
Excessive sedation of the mother
fetal head injury during delivery
aspiration of blood or amniotic fluid
intrauterine hypoxia due to nuchal cord
What maternal disease increases the risk of RDS, and briefly explain the mechanism.
Maternal diabetes
Maternal hyperglycemia –> fetal hyperinsulinism –> suppresses surfactant synthesis.
List 3 risk factors (associations) for RDS.
male sex
maternal diabetes
cesarean delivery
What are the two major complications of RDS?
- Retinopathy of prematurity: treatment with oxygen leads to hyperoxia –> decrease in VEGF; relative hypoxia during weaning off oxygen leads to increase in VEGF, inducing retinal vessel proliferation (neovascularization).
- Bronchopulmonary dysplasia:
- decrease in alveolar septation - large, simple alveolar structures.
- multifactorial.
What are (4) classic histologic features of NEC?
Mucosal or transmural coagulative necrosis
ulceration
bacterial colonization
submucosal gas bubbles
Later: reparative changes - fibrosis and granulation tissue.
What are the two main routes of fetal/perinatal infection?
Transplacental (hematogenous)
Transcervical (ascending)
What are some consequences to the fetus of ascending infection, and what is the mechanims?
Preterm birth: due to rupture of amniotic sac - either due to inflammation, or release of prostaglandins from neutrophils
Pneumonia, sepsis, meningitis: fetus infected via aspiration of amniotic fluid.
Which infections are typically ascending, and which hematologic?
Ascending: HSV2, most bacteria
Hematologic: parasites (toxoplasma), most viral infections, some bacterial (listeria, treponemal)
What are the possible sequelae of Parvovirus B19?
Spontaneous abortion
Stillbirth
Anemia
Hydrops fetalis
What are the possible clinical presentations of TORCH infections?
Fever
Encephalitis
Hepatosplenomegaly
Pneumonitis
Myocarditis
Vesicular & hemorrhagic skin lesions
What organism is the most common cause of early-onset (within first 7 days of life) sepsis?
Group B strep
Define immune hydrops.
Autoimmune hemolytic disease due to RBC antigen incompatibility between the mother and fetus.
Name two consequences of excessive destruction of RBCs due to immune hydrops in the neonate, and discuss their consequences.
Anemia: directly due to red cell loss. leads to liver and cardiac injury due to HYPOXIA. Decreased liver protein synthesis and cardiac failure lead to decreased plasma oncotic pressure and increased hydrostatic pressure, culminating in hydrops.
Janudice: hemolysis –> unconjugated bilirubin –> passes through infant’s weak blood-brain barrier –> water insoluble but fat soluble, binds to lipids in brain –> kernicterus.
list the THREE major causes of NONimmune Hydrops
Cardiovascular defects
Chromosomal anomalies
Fetal anemia
List 3 chromosomal anomalies associated with non-immune hydrops
trisomy 21
trisomy 18
Turner 45, X0
Mechanisms: Turner - defect of lymphatic drainage in the neck –> nuchal hydrops
Trisomies: accompanying cardiac structural defects leading to cardiac failure
List causes of non-immune anemia leading to hydrops.
Alpha-thalassemia
Parvovirus B19
Monozygotic twinning (with twin-twin transfusion)
what is a classic finding in the peripheral blood of a neonate with hydrops ?
Erythroblastosis - large numbers of immature RBCs in the circulation, secondary to extramedullary hematopoesis.
Name two inborn errors of metabolism.
Phenylketonuria
Galactosemia
List 7 clinical manifestations of cystic fibrosis.
Chronic lung disease (secondary to recurrent infections)
Pancreatic insufficiency
Steatorrhea
Malnutrition
Hepatic cirrhosis
Intestinal obstruction / Meconium Ileus
Male infertility.
Define SIDS
Sudden Infant Death Syndrome: sudden, unexplained death of a child <1 year of age that remains unexplained ever after a complete autopsy, examination of the death scene, and review of the clinical history.
What is the ‘triple risk’ model of SIDS?
Vulnerable infant
Critical period of development
Environmental/exogenous stressor
name some postmortem abnormalities that can be detected in cases of sudden unexplained infant death
Infections
viral myocarditis
unsuspected congenital anomaly
Long QT
Anomalous origin of left coronary artery (from left pulmonary artery)
Traumatic child abuse
Intentional suffocation
Congenital aortic stenosis
