Embryology and Teratology Flashcards
1
Q
What is teratogenesis?
A
Production of birth defects
2
Q
What are malformations? Where could they be located? Are they always visible?
A
non-reversible morphological defects present at birth. Could be exterior/internally located or only microscopically visible
3
Q
What is a congenital anomalies and when is it present?
A
It is birth defects, congenital disorders or congenital malformations. Present at birth
4
Q
How many congenital anomalies are present?
A
More than 200
5
Q
Birth defects are present in __-__% of all live births
A
2-3%
6
Q
Birth defects are the leading cause infant death in North America for what 3 reasons?
A
- improvements in obstetrical care
- increased medications and social drug use
- environmental contaminants?
7
Q
In 1996, birth defects were what % of of infant deaths in UP?
A
22.4
8
Q
Why does the incidence of birth defects increase by ___-___% when kids turn 2 y.o.?
A
4-6%
due to discovery of internal organ defects
9
Q
Birth defects account for _____ of all deaths in infants < 1 y.o and ____ of all deaths in children <15 y.o.
A
> 1/3
< 15 y.o.
10
Q
Why aren’t defects noticed at birth a lot of the times?
A
because they are symptomless
11
Q
What make up for 20-25% of the causes of birth defects?
A
known genetic causes and chromosomal abbreviations
12
Q
Maternal illnesses are responsible for what 2 developmental defects?
A
- Infections (2-3%)
2. Metabolic disturbances (1-2%)
13
Q
Drugs and chemicals are the cause of that % of developmental defects?
A
4-5%
14
Q
Susceptibility of teratogenesis heavily influenced by ______ of mother and infant. Nutritional deficiencies play a significant role + genetic susceptibilities.
A
genetics
15
Q
Less than ___ % of all human pregnancies result in healthy normal infants.
A
50
16
Q
What is the largest contributor to unsuccessful pregnancy?
A
post-implantation losses (31%)
implantation: the attachment of the fertilized egg or blastocyst to the wall of the uterus at the start of pregnancy, often delayed in some mammals by several months.
17
Q
What is the organogenic period? What is it synonymous with? When does the organogenic period take place?
A
when ovum divides and differentiates. Teratogenic period - max vulnerability period of the fetus - 15-57 days / 3-8 weeks
18
Q
When does the neural tube close?
A
within 28 days of gestation - most women don’t know they are pregnant - folate is essential for women CAPABLE of becoming pregnant
19
Q
What 3 things take place during the organogenic period (a CRITICAL period)?
A
- cell organization
- cell differentiation
- organogenesis
- Maximal cell division and differentiation
20
Q
What are the two main ways that the body grows during pregnancy?
A
- hyperplasia:
- Increase in cell number
- Time of maximum vulnerability for teratogenic effects
- Day 17-56 after fertilixation - hypertrophy
- hyperplasia ceases
- Risk of development of organ or biochemical malfunctions
- after 8 weeks
21
Q
What happens if there is an interference with hyperplasia?
A
PERMANENT reduction in cell number
22
Q
What is ovulation?
A
ovum expelled by ovary into Fallopian tubes
23
Q
What happens during fertilization?
A
Sperm penetrates oocyte and becomes zygote
24
Q
What is blastogenesis? What does it result in?
A
zygote begins to cleave and increase in cell number. Creation of morula: a solid ball of cells resulting from division of a fertilized ovum, and from which a blastula is formed – a cavity (blastocele) then forms in the centre of the morula and the entire structure is now called a blastocyst!
25
What are the two different cell types within blastocysts?
1. embryo blast (inside)
| 2. trophoblast (outside)
26
What do trophoblast cells secrete and what does this do?
They secrete proteolytic enzymes which erode epithelial uterine lining (in order to create an implantation site for the blastocyst)
27
During the first 20-25 days after conception, how are the nutrients of the blastocyst absorbed? What is this phase called?
Phagocytosis because nothing connecting embryo and mom (no placenta, no fetal circulation yet)
Histiotrophic nutritional phase
28
What do trophoblasts form after the historic nutritional phase (20-25 days)?
a cord of cells called endometrium which starts forming the placenta
29
Pre-implatnation stage:
1. time period?
2. Increase in cell _____ but no increase in cell _____.
3. what is the baby called during this stage?
4. What happens to baby upon exposure to toxicants during this stage?
number, size
1. < 1 week (pre-implantation period)
2. number, size
3. zygote, blastocyst
4. no effect (because cells can be replaced by other ones easily) or lethality (pleuropotency: fate of cells is not determined therefore capable of giving rise to several different cell types and great restorative capacity)
30
What stage follows the pre-implantation stage?
1. Time frame?
2. What starts forming, where?
Gastrulation - embryo development
1. 16 days - at day 14: inner cell mass starts to differentiate into different cell types
2. formation of invagination (Henson's node) in the future cranial area of ectoderm -- moves caudally (from the back) - forms primitive streak (faint streak that is the earliest trace of the embryo in the fertilized ovum)
31
Gastrulation:
1. time period
2. What 3 things form?
3. Teratogen susceptibility?
Cell migration through primitive streak
1. week 2-3
2. formation of 3 germ layers: ectoderm, mesoderm, endoderm
3. very susceptible to teratogens
32
What is each germ layer going to become:
1. Endoderm
2. Mesoderm
3. Endoderm
1. Brain, CNS, skin
2. voluntary muscles, CV and excretory systems
3. Digestive and respiratory systems, glandular organs (exocrine/endocrine)
33
What 3 main events make up the gastrulation phase?
1. Primitive streak = future axis of the embryo --> 3 layers of the embryo
2. Neurulation: ectoderm differentiates into neural plate --> neural tube
3. Mesoderm and endoderm cells migrate internally to form organs and tissues
34
What stage occurs after gastrulation - time period?
Post ovulation -- days 27-29
35
Post-Ovulation:
1. What is established? What vital organ becomes active?
2. Size & weight of embryo?
3. What is the status of the neural tube?
4. What day must neural tube close?
1. general shape of embryo established - heart starts beating
2. < 1 inche & < 1 oz
3. Neural folds fused --> neural tube has segregated into head region and post cranial region
4. day 27 to prevent nerve degeneration
36
What stage occurs after Post-Ovulation?
Organogenesis
37
Organogenesis:
1. Time period?
2. What is established?
3. What 4 things are characteristic of this stage?
4. teratogen susceptibility?
5. Periods of ______ susceptibility for each forming structure.
1. 3-8 weeks
2. organs and body structures established
3. cell proliferation, cell migration, cell-cell interactions & tissue remodelling
4. extremely susceptible to teratogens
5. Maximum
38
What happens at the 8th week of gestation?
What does the fetus get its nutrients from at this point?
FETUS :) All essential and external&internal structures are present
- Placenta has developed and accounts for most nutrient needs
39
What stage occurs after organogenesis?
Fetal/neonatal
40
Fetal/neonatal:
1. Time frame?
2. What happens at this stage?
3. teratogen susceptibility?
1. 8 weeks - birth
2. growth & physical maturation -- little differentiation of organs takes place except external genitalia
3. effects growth and functional maturation: CNS and reproductive abnormalities, behavioural and motor deficits. More functional and growth abnormalities rather than morphological defects
41
What are the 3 classes of teratogens?
1. medications
2. social drugs
3. environmental agents
42
What are 5 examples of medication teratogens?
1. seizure medications
2. Accutane
3. thalidomide
4. lithium
5. chemotherapy drugs
43
What are 4 examples of environmental agent teratogens?
1. organic solvents
2. heavy metals
3. pesticides
4. PCBs (polychlorinated biphenyls)
44
How can teratogenic exposure to certain medications/drugs be diagnosed?
syndrome of the baby
45
What teratogen is responsible for most fetal abnormalities?
alcohol
46
For each drug: associated defects, risk of defect.
1. Dilantin
2. Thalidomide
3. Antineoplastic drugs
4. Diethylstilbestrol
5. Dextromethorphan
1. Fetal hydantoin syndrome (10%)
2. Limb and ear abnormalities (20%)
3. congenital abnormalities (17%)
4. Uterine and cervical defects (22-53%)
5. CNS abnormalities
47
What factors affect severity of tetranogens?
1. type of medication
2. time of exposure
3. length of time of exposure
48
What are the 4 classes of tetratogens?
1. High temperature or fever (sustained exposure to hot tubes - raises core body temp)
2. Infection diseases
3. Chronic diseases
4. Nutrient deficiencies and excesses via dietary intake and through drug intake
49
What are 3 examples of infectious diseases that are classified as teratogens?
1. Rubella
2. cytomegalovirus
3. toxoplasmosis
50
What happens if you intake excess:
1. iodides during pregnancy?
2. fluoride?
3. Vitamin D?
4. Vitamin A?
1. congenital goitre, Mental and physical retardation
2. Spina Bifida Occulta
3. Facial abnormalities, mental retardation
4. CNS abnormalities
51
What is the % of incidence of birth defects according to each daily retinol intake?
1. 0-5000 I.U. (international unites)
2. 5,001-8,000 I.U.
3. 8,001 - 10,000 I.U.
4. > or = to 10,001 I.U.
1. 1.3%
2. 1.6%
3. 2.7%
4. 3.2%
52
In a study conducted, women who took in >10,000 I.U. vitamin A / day saw what increase in risk of neural tube defects?
4.8 times - increased risk closely associated with timing of intake during pregnancy
53
What % of women consume >10,000 I.U. of vitamin A today? As a result, what fraction of babies have birth defects associated with Vitamin A intake?
1.4%
1/57
54
What is the effect of each nutrient deficiency?
1. Protein
2. Vitamin A
3. Vitamin D
4. Vitamin E
5. Vitamin K
1. Microcephaly
2. Eye abnormalities, microcephaly
3. Fetal rickets, hypoplasia of tooth enamel, decreased bone density, growth failure
4. Congenital abnormalities.
5. Coumadin syndrome (anticoagulant, e.g. dicoumarol)
55
Smoking decreases vitamin __ stores - non-specific birth defects and spontaneous abortions
E
56
What is the effect of each nutrient deficiency?
1. Folate
2. Iodine
3. Potassium
4. Copper
5. Zinc
1. neural tube defect - caused by poor diet, maternal drug intake & genetic susceptibility to abnormalities in folate metabolism
2. Cretinism - mental and physical retardation: potbelly, large tongue, facial characteristics of Down's syndrome
3. Kidney abnormalities
4. Connective tissue defects, brain and bone abnormalities.
5. Neural tube defects - cannot mobilize Zn to meet embryonic needs
57
What is the result of genetic inborn errors of Copper metabolism?
Menkes kinky hair syndrome --> major developmental abnormalities in brain, bones, blood vessels
58
What is acrodermatitis enteropathica?
inability to absorb Zn - causes rashes, hair loss, diarrhea & poor growth. Increased risk of birth defects and pregnancy complications
59
_______ is a folate antagonist and causes a __% risk of NTD.
Methotrexate, 30%
60
_____ is a vitamin K antagonist and causes __% risk of congenital heart disease.
Coumadin, 7%
61
Anticonvulsants induce ____ & ____ deficiencies.
Folate, Zinc
62
What are 4 characteristics of Fetal Alcohol Syndrome?
1. Craniofacial dimorphism
2. Growth retardation (head circumference, weight, height < 10th percentile)
3. Decreased fat stores
4. Retarded psychomotor and intellectual development
-Neurological abnormalities, developmental delay, behavioral dysfunction/deficit, intellectual impairment and/or structural abnormalities (microcephaly or brain malformation)
63
What is the leading cause of birth defects and intellectual handicap in North America?
Fetal Alcohol Syndrome
64
The ___ trimester is the greatest sensitivity of the fetal brain.
3rd
65
What are the 4 major facial abnormalities of Fetal Alcohol Syndrome?
1. Short palpebral (re: eyelids) fissures
2. Elongated mid-face
3. Thin upper lip
4. Retrognathia; receding jaw
66
What does it mean by "dose-response relationship" in FAS?
The more you consume the higher the effect
67
If a mother consumes __ oz. absolute alcohol in late pregnancy --> ___ g decrease in birth weight
1 oz.
| 160 g
68
What alcohol consumption from mother puts kid at a high risk of getting fetal alcohol syndrome?
3 oz.
4 drinks / day
or just binge drinking
69
Fetal alcohol syndrom is present in __-__% of children born to alcoholic mother.
30-50%
70
1 dose of ___ drinks very early in pregnancy or av. ___ drinks/day in later pregnancy is associated with learning difficulties.
1. >5
| 2. 2 drinks/day
71
Heavier drinkers have ___%risk of child with FAS & __-__% risk of fetal damage
1. 45%
| 2. 50-95%
72
How many diagnostic criteria (symptoms) of FAS must a baby possess in order to diagnose it as that?
2-3
73
What are 3 alcohol related birth defects? (ABRD)
1. Microcephaly
2. Heart and lung malformations
3. Minor physical abnormalities
74
What are 3 alcohol related CNS disturbances?
1. decreased attention span
2. decreased IQ
3. hyperactivity
75
~ ___% of alcohol is metabolized by the enzyme:
95%
| alcohol dehydrogenase
76
Alcohol crosses placenta ______.
freely
77
Is the half life of alcohol increased of decreased in embryo/fetus?
increased
78
Is detoxification and clearance more or less developed in embryo/fetus?
less
79
After absorption, alcohol is ______ distributed to all body fluids. It crosses the ________ and ________ barriers until at _______ with mother's blood.
1. evenly
2. blood-brain
3. placental
4. equilibrium
80
The fetus and embryo developing CNS is ____ susceptible to alcohol related effects than adult brain.
more
81
Why does alcohol replace calories from other sources?
Because it has a higher caloric value but no nutritional value - displacement of nutrient rich foods from diet
82
How does alcohol affect folic acid and zinc metabolism? What kind of vicious cycle does this cause?
It impairs absorption. Protein and zinc malnutrition enhance effects of alcohol so its a vicious cycle with zinc and alcohol
83
What is alcohol metabolized into?
acetaldehyde which gets converted to acetic acid via aldehyde dehydrogenase
84
why is acetaldehyde even more toxic than alcohol?
it is toxic at uM concentrations vs. mM for alcohol
85
What process does chronic consumption of alcohol prolong?
inflammatory process
86
Depletion of vitamin K via alcohol leads to what?
hypokalemia
87
What are neural tube defects?
congenital abnormalities of the fetal spine and central nervous system - include neural tube defects
88
What develops from the neural tube?
brain and spinal cord
89
What type of disorders do neural tube defects cause?
central nervous system disorders
90
How many people are born with neural tube defects per year?
0.5 million
91
What is anencephaly?
the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. Results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception.
92
What is the difference between exencephaly and anencephaly?
Exencephaly: brain is located outside the skull
Anencephaly: large part of the skull is absent along with the cerebral hemispheres of the brain
93
What happens to babies born with anencephaly or exencephaly?
die shortly after death
94
What is the most common neural tube defect?
Spina bifida
95
What is spina bifida? What are the side effects?
lack of bone encasement of the spine --> permanent spinal cord and spinal nerve damage.
Effects: can't walk, abnormal bladder & bowel function, facility.
96
What are the 9 different etiologies of neural tube defects?
1. multifactorial inheritance (both genetic and envr)
2. single gene (autosomal recessive) disorders
3. chromosomal aneuploidy (Trisomy 13)
4. Teratogens (Valproic Acid, Thalidomide)
5. Maternal IDDM (insulin dependent diabetes)
6. severe overweight
7. family history or prior NTD-affected pregnancy
8. Hot tub/fever in early pregnancy
9. folate deficiency or inborn error of folate metabolism
97
Only __% of NTDs have an identifiable genetic cause.
12%
98
What % of NTDs are related to folate deficiency or abnormal folate metabolism?
50-75%
99
Folate supplements reduce risk of NTD by ___%
71%
100
What is the supplement recommendation of folate for women who previously gave birth to a child with a neural tube defect?
4 mg
101
What & of non-pregnant women don't take folic acid supplements?
71%
102
Fortification is thought to increase intake of folate by how much?
100 ug/day
103
Typical non-pregnant women 19-50 yrs old intake how much folate on average?
137 ug/1000 kcal or ~230 ug
