Developmental Pathology Flashcards
Potter’s Sequence
- Causes: fetal renal agenesis, chronic amnionic fluid leakage secondary to ruptured membranes, fetal urinary tract outflow obstruction
- Phenotype: flattened facies, positional abnormalities (deformations) of hands and feet (talipes equinovarus), hypoplastic lungs, amnion nodosum (squamous metaplasia of amnion)
Drugs/chemicals that are teratogenic
Thalidomide
• Previously used as tranquilizer; now as anti-neoplastic agent
• Causes limb abnormalities (50-80%)
• Downregulates wingless (WNT) signaling
Valproic acid = anti-epileptic
• Disrupts homeobox (HOX) transcription factor proteins
• Role in limb, vertebral, and craniofacial structure patterning
Vitamin A (Retinol) • Deficient and excess amounts = teratogenic • Retinoic acid embryopathy = CNS, cardiac, craniofacial defects (cleft lip/palate) • Disrupts TGF-β signaling
Alcohol embryopathy/Fetal Alcohol syndrome
Others: • Folate antagonists (anti-cancer agents) • Androgenic hormones • Dilantin (anti-seizure medication) • Warfarin (prevent blood clotting)
Toxoplasmosis
- Infected: consumption of undercooked meat, cat feces
- Transplacental (hematogneous) infection
- Result: fetal periventricular brain calcifications and chorioretinitis
- Increased risk of infection with increased gestational age BUT increased severity of disease with earlier age
“O” in TORCHES
o Others: varicella-zoster, influenza, mumps, HIV, enterovirus
Rubella (German Measles)
- Infection: first 16 weeks; most sensitive time: 1st 8 weeks
- Congenital Rubella Syndrome: (tetrad) cataracts, heart defects (especially PDA), deafness, mental retardation
CMV infection
- Asymptomatic to mother
- Most serious time of infection = 2nd trimester
- Results: mental retardation, microcephaly, deafness, hepatosplenomegaly, fetal death
Characterized:
• Chronic villitis (but non-specific)
• Viral intranuclear inclusions (“owl’s eye”)
HSV Type 2
• Transmitted during birth
Herpes neonatorum:
• Limited: skin, eye, mucous membranes (SEM disease)
• Dismmeninated: liver (necrotizing hepatitis), brain (encephalitis), high mortality rate
Syphilis
• Spirochete Treponema pallidum crosses placenta
Early (infantile) manifestation:
• Occurs in 1st 2 years of life
• “Snuffles” (nasal discharge and congestion
• Bullous skin rash
• Hepatomegaly (fibrosis)
• Skeletal abnormalities (saddle nose, saber shins)
Late (tardive) manifestation:
• Either following infantile form or alone
• Hutchinson Triad: notched central incisors, interstitial keratitis with blindness, deafness (8th CN injury)
Radiation
o Exposure during organogenesis (1st trimester) → microcephaly, blindness, skull defects, spina bifida, others
o Early exposure = worse than later gestational exposure
Fetal alcohol spectrum disorders (FASDs)
Distinctive facial appearance
• Microcephaly
• Maxillary hypoplasia
• Short palpebral fissures
o Growth retardation
o Cardiac defects (atrial septal defects)
o Psychomotor abnormalities
Fetal Alcohol Syndrome: needs 3 characteristics:
• Growth retardation
• Facial anomalies
• CNS dysfunction
Maternal diabetes
(poorly controlled) → Diabetic embryopathy
o Large for gestational age infants (macrosomia)
• Higher risk for birth injury
o Congenital heart defects
o Neural tube defects (spina bifida)
o CNS malformations
o Pancreatic islet cell hyperplasia
o After delivery = can have severe hypoglycemic episodes
Also associated with transposition of Great Vessels
Non-immune hydrops: 3 major causes:
o Cardiovascular defects
o Chromosomal anomalies (Turners syndrome)
o Non-immune fetal anemia (Parvovirus B19/hemoglobinopathy)
Associated with numerous other conditions
Prune Belly syndrome:
o Predominantly males o Due to urethral obstruction (multifactorial cuases) o Massively dilated bladder, hydronephrosis (dilation of renal pelves and calices) o Renal cystic medullary dysplasia o Enlarged wrinkled (prune-like) abdomen • Thin or absent abdominal musculature o Cryptorchidism (undescended testicle) o Hypoplastic prostate
Differentiate between transcervical (ascending) and transplacental (hematologic) perinatal infections. Describe the pathogenesis of fetal parvovirus B19 infection.
Transcervical:
o Usually bacterial
o Lead to chorioamnionitis and premature birth
o May cause premature rupture of membranes
Transplacental:
o Lead to IUGR, mental retardation, cataracts, congenital heart defects, bone defects
o Most = viral or parasitic
***Parvovirus B19: replicates in RBC precursors → destruction → severe anemia, hydrops, increased extramedullary hematopoiesis
• Histo: Smudge look of cells
o Can be bacterial (Listeria, Treponema)
Time of delievery = see chronic villitis
• Histologic evidence of infection
• Inflammatory cells (lymphocytes, rarely plasma cells) in villi and intervillous space
• But: >1/2 causes of chronic villitis are unknown (villiits of unknown etiology: VUE)
• Assumed to represent autoimmune process
• Associated with IUGR and stillbirth
Chorioamnionitis
o Acute inflammation of fetal membranes due to maternal immune response (maternal neutrophils in fetal membranes)
o Neutrophils release cytokines → PROM
o TLR’s bind bacterial components → dysregulate prostaglandins → uterine smooth muscle contraction
o Result: premature delivery
o Complications: premature lungs (RDS) or infection
