2) Embryology and Teratology (Part II) Flashcards
Methotrexate is a _______ antagonist.
folate
What is methotrexate associated with?
30% risk of NTD
Coumadin is a _________ antagonist.
vitamin K
Which nutrient deficiencies are anti-convulsants associated with?
Folate and zinc deficiencies
What is fetal alcohol syndrome?
Collective term to describe a set of features associated with infants exposed to alcohol during pregnancy
What is fetal alcohol syndrome characterized by?
- Craniofacial dimorphism (palpebral eyelid fissures, elongated mid-face, thin upper lip)
- Growth retardation
- Retarded psychomotor and intellectual development
What is the leading cause of birth defects and intellectual handicap in North America?
Fetal alcohol syndrome
Which trimester of pregnancy confers the greatest sensitivity of the fetal brain to FAS?
The third trimester
What characterizes a high risk for FAS?
- 3 ounces of alcohol per day
- Or, 4 drinks per day
What characteristics determine the risk of FAS?
- Quantity of alcohol
- Frequency of drinking
- Timing of the consumption of alcohol during pregnancy
How is FAS diagnosed?
2 of the 3 diagnostic criteria must be present
What are characteristics of alcohol-related birth defects (ARBD)?
- Microcephaly
- Heart and lung malformations
- Minor physical abnormalities
ARBD occurs in the absence of what?
Apparent neurobehavioral or brain disorders
What are characteristics of CNS disturbances due to alcohol?
- Decreased attention span
- Decreased IQ
- Hyperactivity
95% of alcohol is metabolized by ____________.
alcohol dehydrogenase
What is the primary region where alcohol is metabolized? Where is it also metabolized?
- Primarily metabolized in the liver
- Also, metabolized in the stomach, which reduces the quantity of active alcohol within the blood
Why may men consume twice the amount of alcohol as women?
- Because they possess twice the amount of alcohol dehydrogenase
- Also, women have a lower body weight than men, so the alcohol consumed is distributed at a higher concentration in the blood
What occurs to alcohol after absorption? How does that affect pregnant women?
- Alcohol is evenly distributed to all bodily fluids, crossing the blood-brain and placental barriers until reaching equilibrium with the mother’s blood
- The equilibrium with the placenta occurs almost immediately
Why is the half-life of alcohol increased in the embryo/fetus?
- The embryo/fetus has decreased blood detoxification abilities due to their limited organ development
- There is very little alcohol dehydrogenase within the placenta
Why is the fetus more susceptible to alcohol-related effects?
- Their developing CNS is more susceptible to alcohol-related effects than the adult brain
- On a body-weight basis, the fetus is also more susceptible than the mother to alcohol
Which nutrient deficiencies is alcohol associated with? How does that affect pregnancy?
- Folate and zinc deficiencies
- In pregnancy, the ingestion of alcohol decreases folate available for the fetus
Which nutrient deficiencies enhance the deleterious effect of alcohol?
Protein and zinc deficiencies
How is alcohol association with potassium?
A heavy consumption of alcohol may deplete potassium stores, which results in hypokalemia
Describe alcohol metabolism.
1) Alcohol is metabolized into acetaldehyde by alcohol dehydrogenase
2) Acetaldehyde is metabolized into acetic acid by acetaldehyde dehydrogenase
What is produced alongside acetic acid during alcohol metabolism?
Free radicals (inflammatory process)
How does the toxicity of alcohol compare to acetaldehyde?
- Alcohol is toxic at mM concentrations
- Acetaldehyde is toxic at uM concentrations
What are the molecular effects of alcohol toxicity on the developing fetus?
- Excessive cell death (apoptosis) in sensitive cell populations
- Placental toxicity
- Fetal hypoxia
What are NTDs?
General term for congenital abnormalities of the fetal spine and CNS, including defects of the neural tube
What are NTDs due to? What determines the type of NTD?
- NTDs are due to disruptions in the orderly formation of the neural tube during gestation
- The type of NTD depends on the region where the NTD occurs