Embryology

Question 1

Produced at base of limbs in zone of polarizing activity. Involved in patterning along anteroposterior axis and CNS development; mutation can cause holoprosencephaly

Answer 1

Sonic hedgehog gene

Question 2

Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb). Necessary for proper organization along dorsal-ventral axis.

Answer 2

Wnt-7 gene

Question 3

Produced at apical ectodermal ridge. Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.

Answer 3

FGF gene

Question 4

Involved in segmental organization of embryo in a craniocaudal direction. Code for transcription factors. ____ gene mutations –> appendages in wrong locations.

Answer 4

Homeobox (Hox) genes

Question 5

Early fetal development:

• Within week 1
• Within week 2
• Within week 3
• Weeks 3-8 (embryonic period)
• Week 4
• Week 6
• Week 8
• Week 10

Answer 5

• Within week 1:
  
  • hCG secretion begins around the time of implantation of blastocyst
  • Blastocyst “sticks” at day 6
• Within week 2:
  
  • Bilaminar disc (epiblast, hypoblast)
  • 2 weeks = 2 layers
• Within week 3
  
  • Gastrulation forms trilaminar embryonic disc.
  • Cells from epiblast invaginate –> primitive streak –> endoderm, mesoderm, ectoderm (3 layers); overlying ectoderm becomes neural plate
• Weeks 3-8 (embryonic period)
  
  • Neural tube formed by neuroectoderm and closes by week 4
  • Organogenesis
  • Extremely susceptible to teratogens
• Week 4
  
  • Heart begins to beat
  • Upper and lower limb buds begin to form
• Week 6
  
  • Fetal cardiac activity visible by transvaginal U/S
• Week 8
  
  • Fetal movements start.
  • Gait at week 8.
• Week 10
  
  • Genitalia have male/female characteristics

Question 6

ACEi

Answer 6

Renal damage

Question 7

Alkylating agents

Answer 7

Absence of digits, multiple anomalies

Question 8

Aminoglycosides

Answer 8

Ototoxicity

Question 9

Antiepileptic drugs

(Valproate, carbamazepine, phenytoin, phenobarbital)

Answer 9

Neural tube defects, cardiac defects, cleft palate, skeletal abnormalities (e.g., phalanx/nail hypoplasia, facial dysmorphism)

**High-dose folate supplementation recommended.

Question 10

DES

Answer 10

Vaginal CCA, congenital Mullerian anomalies

Question 11

Folate antagonists

(Trimethoprim, methotrexate, antiepileptic drugs)

Answer 11

Neural tube defects

Question 12

Isotretinoin

Answer 12

Multiple severe birth defects

**Contraception mandatory

Question 13

Lithium

Answer 13

Ebstein anomaly (apical displacement of tricuspid valve)

Question 14

Methimazole

Answer 14

Aplasia cutis congenita

Question 15

Tetracyclines

Answer 15

Discolored teeth, inhibited bone growth

Question 16

Thalidomide

Answer 16

Limb defects (phocomelia, micromelia–“flipper” limbs)

Question 17

Warfarin

Answer 17

Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities

**Use heparin!! Does not cross the placenta**

Question 18

Alcohol

Answer 18

Common cause of birth defects and intellectual disability; fetal alcohol syndrome (leading cause of intellectual disability in the US)

• smooth philtrum, thin vermillion border, small palpebral fissures

Mechanism is failure of cell migration

Question 19

Cocaine

Answer 19

Low birth weight, preterm birth, IUGR, placental abruption

Cocaine –> vasoconstriction

Question 20

Smoking (nicotine, CO)

Answer 20

Low birth weight (leading cause in developed countries), preterm labor, placental problems, IUGR, SIDS

Nicotine –> vasoconstriction

CO –> impaired O2 delivery

Question 21

Iodine (lack or excess)

Answer 21

Congenital goiter or hypothyroidism (cretinism)

Question 22

Maternal diabetes

Answer 22

Caudal regression syndrome (anal atresia to sirenomelia - Mermaid syndrome), congenital heart defects, neural tube defects, macrosomia

Question 23

Methylmercury

Answer 23

Neurotoxicity

Highest in swordfish, shark, tilefish, king mackerel

Question 24

Vitamin A excess

Answer 24

Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac)

Question 25

X-rays

Answer 25

Microcephaly, intellectual disability Minimized by lead shielding

Question 26

Dizygotic ("fraternal") twins vs. Monozygotic ("identical") twins

Answer 26

Dizygotic ("fraternal") twins: arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes) and will have 2 separate amniotic sacs and 2 separate placentas (chorions). Monozygotic ("identical") twins arise from 1 fertilized egg (1 egg + 1 sperm) that splits in early pregnancy. The timing of cleavage determine chorionicity (number of chorions) and amnionicity (number of amnions).

Question 27

Placenta * Purpose? * Fetal component? * Maternal component?

Answer 27

Placenta * Purpose? * Primary site of nutrient and gas exchange between mother and fetus * Fetal component? * **Cytotrophoblast:** Inner layer of chorionic villi (**c**ytotrophoblast makes **c**ells) * **Syncytiotrophoblast:** Outer layer of chorionic villi; synthesizes and secretes hormones, e.g., hCG (structurally similar to LH); stimulates corpus luteum to secrete progesterone during first rimester * Lacks MHC-I expression --\> decrease chance of attack by maternal immune system * Maternal component? * Decidua basalis: * Derived from endometrium * Manternal blood in lacunae

Question 28

Umbilical cord

Answer 28

**Umbilical arteries (2)** - return deoxygenated blood from fetal internal iliac arteries to placenta \*\*Single umbilical artery (2-vessel cord) is associated with congenital and chromosomal anomalies\*\* **Umbilical vein (1)** - supplies oxygenated blood from placenta to fetus; drains into IVC via liver or via ductus venosus

Question 29

Umbilical arteries and vein are derived from \_\_\_\_\_\_\_\_\_\_.

Answer 29

Allantois

Question 30

**Urachus:** In the 3rd week, the yolk sac forms the allantois, which extends into urogenital sinus. Allantois becomes the urachus, a duct between the fetal bladder and umbilicus. Patent urachus: Urachal cyst: Vesicourachal diverticulum:

Answer 30

* **_Patient urachus:_** Total failure of urachus to obliterate --\> urine discharge from umbilicus * **_Urachal cyst:_** Partial failure of urachus to obliterate; fluid filled cavity lined with uroepithelium, between umbilicus and bladder... can lead to infection, adenocarcinoma\*\* * **_Vesicourachal diverticulum:_** Slight failure of urachus to obliterate --\> outpouching of bladder

Question 31

**Vitelline duct:** 7th week--obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen Vitelline fistula: Meckel diverticulum:

Answer 31

* Vitelline fistula: * Vitelline duct fails to close --\> meconium discharge from umbilicus * Meckel diverticulum: * Partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum). May have heterotopic gastric and/or pancreatic tissue --\> melena, hematochezia, abdominal pain