lectures extra questions Flashcards
(191 cards)
1
Q
What are autosome?
A
chromosomes 1-22
2
Q
What are the 4 stages of gametogenesis?
A
migration + mitosis
meiosis (I+II)
Maturation
3
Q
How many primary oocytes are made in mitosis in females?
A
7million (peak month 5)
40,000 at puberty (due to degen.)
4
Q
What is the difference between sister chromatids and homologous chromosomes?
A
Sister chromatids = split in M2
Homologous chromosomes = split in M1
5
Q
What is dictyate?
A
primary oocytes arrest in prophase I
6
Q
What is the secondary oocyte arrested in before fertilisation?
A
metaphase II
7
Q
what are the 2 commonest teratomas?
A
sacrococygeal > oropharyngeal
8
Q
What is a translocation? What are the two types? What is the most common translocation?
A
Where part of 1 chromosome breaks off and joins another chromsome (commonest = 14–>21)
Balanced
Unbalanced
9
Q
What are the 3 causes of T21?
A
95%: non-dysjunction (M1 most between homologous chromosomes and M2 less common between sister chromatids)
4% unbalanced translocation
1% mosaicism
10
Q
What are the causes of aneuploidy?
A
Unbalanced translocation
mosaicism
Non-dysjunction
11
Q
What is non-dysjunction?
A
Missegregation of chromsomes during M1 or M2 (meiosis)
12
Q
What is mosaicism? Use it to explain why there might be different severities of T21?
A
Missegregation of chromsomes during mitosis (of the zygote)
Causes 2 cell populations –> some normal and some trisomy
13
Q
Clinical features of Down’s?
A
Learning disability
14
Q
Clinical features of Down’s?
A
Learning disability, single palmar creese, brushfield spots, small mouth, protruding tongue, low birth weight,
15
Q
Clinical features of turner’s?
A
Characteristically female, webbed neck, wide-spaced nipples, lymphoedema, short, no ovaries
16
Q
Complications of Down’s
A
CHD (VSD), early onset dementia, hypothyroid, coeliac, constipation, refluc, cataract, glaucoma
17
Q
What cardiac defect is Turner’s linked to?
A
coarctation of the aorta
18
Q
What complications are associated w/ turner’s?
A
infertile (no ovaries), coarctation Ao
19
Q
What is the usual cause of Turner’s?
A
Non-dysjunction in spermatogenesis
20
Q
How do sperm mature?
A
condensation of the nucleus, formation of the acrosome, formation of the neck/middle piece/tail –> shedding of the cytoplasm
21
Q
What is inadequate implantation of the blastocyst linked to?
A
PROM, pre-eclampsia, IU fetal death, IUGR, preterm, placental abruption
22
Q
describe fertilisation
A
corona radiata then ZP penetration –> fusion of cell membranes of oocyte + sperm –> oocyte completes M2
23
Q
What does the sperm undergo in the female tract?
A
Capacitation
acrosome reaction (when it binds to ZP)
24
Q
Give 3 female structural causes for abnormal implantation / subfertility?
A
Fibroids
Congenital uterine defects
endometriosis
25
How many pregnancies are ectopic?
2%
26
What is an ectopic?
Extra-uterine pregnancy
27
if a women has an endocrine disorder (PCOS), how might you induce ovulation?
1. clomiphene citrate
2. GnRH analogue (PULSATILE) + hCG
3. FSH/LH + hCG
28
What does hCG do in inducing ovulation + IVF?
It causes an LH surge + causes woman to ovulate
29
How does clomiphene citrate work?
Oestrogen antagonist
Suppresses the -ve feedback to hypothalamus + pituitary
Causes ^ GnRH --> ^ FSH/LH
30
What are the steps of IVF?
1. Induction of ovulation / gamete production
2. gamete retrieval (including sperm)
3. IVF (culture dish + incubated)
4. embryo culture until 8 cell stage
5. embryo transfer
31
What drugs do you use to induce ovulation in IVF?
Leuprolide acetate (GnRH agonist)
FSH daily
hCG
32
What's the alternative to IVF in women who have PCOS? Why would you do this?
In vitro gamete maturation
PCOS at high risk of OHSS and this method doesn't use ovulation stimulation step of IVF
33
What is the basic principle behind ovarian hyperstimulation syndrome?
^ oestrogen (a powerful vasodilator) --> fluid shift extravascular compartment
34
How can you preserve embryos and gametes?
freezing/cryopreservation using cryoprotectant chemicals (prevent ice crystals forming)
35
Who is IVF indicated for?
Tbal disease, endometriosis, mild male infer, unexplained infertility
36
Who is IVF contraindicated in? What might you use?
Severe male infertility --> ICSI (intracytoplasmic sperm injection)
PCOS --> in vitro gamete maturation
37
Define severe male infertility?
Problems w/ sperm morphology, motility and low sperm count (or non-obstructive azospermia)
38
How might a male with obstructive azospermia have sperm obtained?
PESA
TESA
39
What are the 3 fates of the epiblast cells?
o Stay put ectoderm
o Form new layer between epiblast + hypoblast mesoderm
o Displace hypoblast cells endoderm
40
what factor is produced cranially and what does it do?
HNF-3beta
specifies brain regions
41
What is the pathway that establishes left sidedness?
5HT (expressed L) --> FGF8 --> Nodal + Lefty 1+2 --> PITX2 (establishes left sidedness)
42
what gene products are produced on the right of the bilaminar disc?
SHH (inhibits left-sided products)
| SNAIL
43
where is Brachyury produced and what does it do?
L/R of primitive node
what it does:
1) ANTEROPOSTERIOR/cranio-caudal patterning --> mesoderm development middle/caudal regions
2) essential for nodal + lefty 1+2 expn
44
What occurs if there is absence/problem w/ brachyury?
Caudal dysgenesis
no anteroposterior patterning
Failure of formation of caudal mesoderm structures --> limbs fused/unformed, urogenital problems)
45
What is caudal dysgenesis associated w/?
Maternal DM
46
What is HPE associated w/?
^ Alcohol intake
47
What is caudal dysgenesis?
AP shortening due to brachyury dysfunction --> loss of caudal middle mesoderm development
SIRENOMELIA
48
What is HPE? What are some features?
Midline defect - deficiency of midline tissues
Single midline ventricle, fused/underdeveloped forebrain, eyes fused midline, narrow head, absent nose...etc
REMEMBER: HPE is an example of aberrant gastrulation
49
What causes laterality problems (situs inversus)?
PITX2 ectopic production R
5HT pathway disruption (SSRIs)
Retinoic acid analogues (isotretinoin)
50
What do 20% of people w/ situs inversus have?
Kartanger's syndrome
51
Give 4 examples of aberrant gastrulation?
1. caudal dysgenesis
2. Situs invertus / laterality seqyences
3. HPE
4. Teratomas
52
What occurs on day 16-18 of heart development?
progenitor heart cells migrate to lateral plate mesoderm + become PHF
53
What does the primary heart field give rise to?
Atria, LV and most of RV
54
What inhibits heart development?
WNT proteins
55
What patterning induces heart development?
BKP expn + WNT blocking substances (from endothelial cells) --> NKX2.5 expressed (master gene for heart developemnt)
NKX2.5 Upregulates Hand 1 + 2 expn --> cardiac looping
5HT, PITX2 and retinoic acid involved in establishing L/R patterning
retinoic acid also specifies caudal structures / atria
56
What is the role of NKX2.5
MASTER HEART GENE
1. Causes Primary HF to become cardiogenic region (myoblast proliferation)
2. Upregulates Hand 1 + 2 expn --> cardiac looping
57
What occurs on day 20-21 of heart development
2HF appears (regulated by NCCs) --> outflow tracts + rest of RV
58
What occurs day 23-28 heart development? how does it occur?
Heart tube dilatations and LOOPING happens
NKX2.5 --> upregulates Hand 1+2 (involved in cardiac looping)
59
What substances are involved in cardiac looping?
Hand 1 + 2
60
How would you treat HF in babies?
1. duct dep: PGs
2. diuretics
3. NG tube
4. O2
5. Upright
61
What is the most common ASD?
High septal ASD (ostium secundum defect)
62
When do pts w/ ASD usually present?
30s/40s w/ HF/atrial arrhythmias
63
What is total anomalous pulmonary venous return?
Pulmonary veins drain into RA therefore survival only if ASD or PDA
64
What are the 4 features of hypoplastic LH syndrome?
1. Underdeveloped LV
2. ASD
3. PDA
4. Small aorta
65
How have some pre-natal screening methods been developed?
markers for disease produced by placenta or fetus (increased or decreased compared to normal pregnancy)
66
Why would you screen?
- manage remaining pregnancy
- Parents can plan
- decide whether to continue pregnancy or not
- plan for labour complications or complications of fetus
- find conditions that affect future preg (e.g. Rh)
67
What is the percentage of false +ves in combined test?
What is its detection rate?
5%
80%
68
When do you do the combined test? What is it comprised of?
10-14w (1st trimester) (11-14 NT)
nuchal translucency (US) + PAPP-A / hCG
69
What is important for 2nd trimester testing?
Need fetal age for accurate intepretation
70
What is involved in 2nd trimester screening?
quadruple test: AFP, Estriol e3, hCG, Inhibin A
triple test: without estriol 3 (do for Edward's)
71
when do you do 2nd trimester screening?
15-22 weeks
72
What are the results for in Down's?
AFP: decreased
E3: decreased
hCG: increased
Inhibin A: increased
73
When is nuchal translucency performed?
11-14 weeks
74
How can you estimate gestational age from US?
crown rump length > baparietal diameter + femoral length
75
What can you use US for in pregnancy?
1. detect multiple pregnancy
2. detect/monitor fetal anomaly
3. monitor preg. in maternal disease
4. placental localisation / problems
5. estimate GESTATIONAL AGE
76
What are the indications for diagnostic tests in pregnancy?
1. screening suggests ^ risk
2. mother >35
3. previous child w/ abnormality
4. parent w/ chromosomal disorder
77
When are CVS and amniocentesis carried out?
CVS: 10-12 weeks
Amnio: 15-16 weeks
78
What are the risks of miscarriage CVS and amniocentesis?
CVS: 1-2%
Amnio: 0.5-1%
79
Give 4 risks of amniocentesis?
Club foot
miscarriage
injury to fetus
Rh sensitisation reaction (give Anti-D)
80
How is karyotyping carried out?
cells from CVS or amnio cultured --> colchicine + hypotonic soln --> spread on slides / giesma stained --> light microscopy
81
What are the types of bands seen on karyotyping?
Light bands: euchromatin (GC rich - many genes)
Dark bands: heterochromatin (AT rich - less genes)
82
What does FISH use? What is it useful for?
Fluorescent antibody/probs which attach to specific parts of the genome
Useful for identifying small chromosomal abnormalities (but need to know what you're looking for)
83
What is pre-implantation genetic diagnosis?
Used in IVF in high risk couples --> blastomere removed at 6-10cell stage to determine if viable
84
When can non-invasive prenatal testing / diagnosis be used and why?
4-5 weeks as fetal DNA found in maternal serum from as early as this
85
is NIPT available on the NHS?
No - only private
86
What are the advantages and disadvantages of NIPT?
Non-invasive, 98% accuracy (only 80% for normal), 0.3% false +ves (5% standard), higher PPV than standard
Problem: invasive testing still required
87
What can NIPD be used to diagnose? Is it diagnostic for everything?
DMD, CAH, Rh, fetal sex, achondroplasia
No - Amnio or CVS needed for some conditions
88
at the 20w anomaly scan, what blood tests are also done?
Triple test (AFP, E3, hCG)
89
When is open fetal surgery carried out for NTDs?
18 weeks
90
how do you prevent preterm labour in open fetal surgery?
Tocolytics
91
How do you maintain intrauterine pressure in open fetal surgery?
fluid cont. pumped into uterus
92
What are some risks of open fetal surgery?
uterine rupture, infection, preterm delivery, fetal death, bleeding
93
Give some uses of fetoscopic fetal surgery?
TTTS+TRAP, CDH, UT obstruction
experiemntal: amniotic band syndrome
94
When does neuralation occur?
week 3 --> neural plate rolls up and 2 folds fuse --> neural tube
95
Where is the commonest region for spina bifida?
Lumbosacral region
96
Give some symptoms of myelomeningocele?
Paralysis / sensory loss (lower limb), bladder dysfunction, UTIs, bowel dysfunction, cognitive defects as hydrocephalus
97
how many spina bifida pts have hydrocephalus?
15%
98
What are the main advantages of pre-natal compared to post-natal NTD repair?
Adzick (2011) study stopped as astonishing results found --> less CSF shunts needed, less patients had lower limb neurological defecit (x2 motor function), less deaths
99
How do congenital diaphragmatic hernias occur?
failure of one or both pleuro-peritoneal membranes to close the pericardio-peritoneal cavities
100
What are congenital diaphragmatic hernias associated with?
50% NTD
| T18
101
What are the feature of congenital diaphragmatic hernia?
respiratory distress + cyanosis,
102
How does FETO work?
Fetoscopic endoluminal tracheal obstruction --> causes fluid to build up and therefore pressure w/in the lung and promote its development
103
What Would you recommend to treat CDH?
Post-natal as a small study (n=23) found no benefit of FETO over post-natal repair in pts --> post-natal repair has less risks (PRETERM DELIVERY)
104
when do the major changes of the placenta take place?
Week 9
105
What is the importance of chorionic villi?
They invade the intervillous spaces (filled with maternal blood) to establish maternal/fetal blood barrier for exchange of gases/nutrients...etc
106
What supplies and drains the intervillous spaces?
Spiral arteries
Endometrial veins
107
What does the mother receive from the fetus across the barrier?
creatinine, uric acid, urea, fetal rbc's (rh Ag), hormones
108
What does the syncitiotrophoblast produce?
hCG, Somatomammotropin, oestrogen, progesterone
109
What occurs on day 6 of placental development?
Blastocyst approaches uterine wall
110
What occurs on day 7 of placental development?
implantation occurs (starts invasion by cytotrophoblasts --> some differentiate to form syncitiotrophoblasts [outer])
111
What occurs on day 8 of placental development?
ST continues to invade --> same time amniotic cavity forms in epiblast layer
112
What occurs on day 9 of placental development?
BC fully embedded, hypoblast proliferates + lines inner CT (extracoelemic membrane), lucunae form in the ST
113
What occurs on day 11-12 of placental development?
ST lacunae fuse --> intervillous spaces (cont. w/ maternal spiral artery capillaries) --> hypoblast new cell pop. (extraembryonic mesoderm) between the hypoblast + CT
114
What occurs on day 12-13 of placental development?
Spaces form + fuse in extraembryonic mesoderm; primary chorionic villi projection form (mesoderm not inside)
115
What occurs on day 13-15 of placental development?
extraembryonic mesoderm invades primary chorionic villi --> forms secondary chorionic villi
116
What occurs on day 21 of placental development?
(extraembryonic) Mesoderm core in the CT differentiates to form blood vessels
117
What does the cytotrophoblast anchor to in the endometrium?
Decidua
118
What is the (extraembryonic) mesoderm core come from in the chorionic villi?
Hypoblast cells that have differentiated to form a new cell population
119
What happens to the extraembryonic mesoderm core in secondary villi on day 21?
differentiate to become blood vessels forming tertiary chorionic villi (contain blood vessels)
120
How much blood do 100 spiral arteries deliver?
150ml/min
121
How does hydrops fetalis occur?
in haemolytic disease of the newborn there is haemolysis of fetal RBCs --> anaemia --> ^ HR --> HF
122
What is the incidence of dizygotic twins?
1/80 pregnancies and accounts for 90% of twinning
123
What are the two unusual types of dizygotic twinning?
Heteropaternal superfecundation
Superfoetation
124
What is the incidence of monozygotic?
3/1000 pregnancies
125
How might monozygotic twinning occur?
Hall (2013) --> ZP damage, ICM damage, blastocyst mosaicism
126
What is the incidence of non-identical and identical triplets?
Non: 1/1000
identical: 1/10,000
127
What are the percentages of the different types of membranes in MONOZYGOTIC twins?
Dichorionic diamnotic: 25-30%
Monochorionic diamniotic: 70-75%
Monochorionic monoamniotic: 1-2%
128
When does splitting of monoxygotic twins occur in Dichorionic diamnotic?
0-3days - 2 cell stage
129
When does splitting of monoxygotic twins occur in Monochorionic diamniotic?
4-7days - early blastocyst
130
When does splitting of monoxygotic twins occur in Monochorionic monoamniotic?
7-14days (after the amnion has developed on d 7) - late blastocyst
131
What are the percentages of the different types of membranes in DIZYGOTIC twins?
Dichorionic diamnotic: 58%
| Monochorionic diamniotic: 42%
132
What are the risks of monochorionic twins / shared placenta?
1. TTTS
| 2. TRAP
133
What % does TTTS + TRAP occur in monochorionic twinning?
TTTS (10-15%)
| TRAP (1%)
134
What are the risks of monoamniotic twinning?
Entanglement and compression of the cord
135
What is the difference between conjoined and parasitic twinning?
Conjoined is symmetrically joined
| Parasitic: unsymmetrical
136
give 4 types of abnormal twinning
1. Vanishing twin
2. Fetus in fetu
3. conjoined twins
4. parasitic twin
137
What is the incidence of conjoined twinning
1/250,000 births
138
What is a risk factor for vanishing twin?
IVF (1/10)
139
What causes conjoined twinning?
PARTIAL splitting after the primitive streak has formed
140
how can you distinhuish fetus in fetu from a teratoma?
contained in amniotic sac, recogn. features (e.g. limbs), covered in skin, attached to dom. twin via pedicle
141
What is epigenetics?
The study of modifications to DNA that alters gene transcription
142
What 2 epigenetic modifications are seen?
Histone acetylation - opens up DNA to allow transcription/expn
DNA methylation - activates or inactivates genes
143
What are the pharyngeal arches made from?
Ectoderm (outer) --> mesoderm core w/ NCCs --> endoderm
144
What cranial nerves do pharyngeal arches 1-4 give rise to?
1: V
2: VII
3: IX
4: X
145
What does pharyngeal arch 1 give rise to?
maxillary + mandibular prominences
146
What does the 1st pharngeal cleft give rise to?
EAM
147
What does pharyngeal arch 2 give rise to?
hyoid bone
148
What do pharyngeal arches 3+4 give rise to?
pharyngeal and neck tissues
149
In the pharyngeal arches waht factors does the ENDODERM produce? What do these do?
BMP7, SHH, PAX1, FGF8
Causes mesenchyme core to express HOX genes
150
What does the mesenchyme core do?
expresses HOX genes (patterning)
151
What forms at the end of week 4 in facial development?
Facial prominences:
- Frontonasal prominences (w/ 2 lateral nasal placodes)
- maxillary prominence
- mandibular prominence
152
What do maxillary + mandibular prominences arise from?
Pharyngeal arch 1
153
What happens on week 5 of facial development?
L/R nasal placodes form nasal pit --> splits into medial and lateral nasal prominences
Maxillary process grows medially --> pushes medial nasal prominences medially + they fuse
154
What forms the secondary palate?
Lateral palatal shelves + maxillary prominences fuse
155
How does the nasolacrimal duct form?
nasolacrimal groove separates the maxillary prominences from the lateral nasal prominences --> endoderm floor thickens forming duct
156
What is DiGeorge syndrome?
What are some features?
Microdeletion chromosome 22
Low set ears, short filtrum, nasal cleft, absent thymous/parathyroids, poor t cell functioon, CHD, learning disability
157
What are the two first arch syndromes?
1. Robin sequence
| 2. Treacher Collins syndrome
158
What is the incidence and pattern of inheritence in Robin sequence in robin sequence?
1/8500
Autosomal dominant
159
What is the cause of treacher collins?
A.D. (60% new mutations) --> TCOF1 gene (product treacle --> NCC differentiation)
160
What are some features of robin sequence?
micrognathia/mandibular hypoplasia, classic U shaped CP, ear/eye defects
161
why do you get a classic U shaped cleft palate in robin sequence syndrome?
Due to micrognathia --> posterior tongue displacement so lateral palatal shelves can't fuse
162
What are some features of treacher collins syndrome?
Micrognathia, external ear malformation, down slanting palpebral fissure, zygomatic/mandibular hypoplasia (micrognathia)
163
What is the incidence of cleft palate?
1/700-1000
164
what types of Cleft palate are there?
in terms of incisive foramen?
1. Anterior (deficiency in mesenchyme of maxillary prominence + medial palatal shelves)
2. Posteiror (palatal shelves don't fuse
165
What is the main cause of cleft palate?
SMOKING (other: syndromic, genetic, anti-epileptic, benzos, rubella)
166
What are the problems associated with cleft palate?
cosmesis, bullying, parent guilt/anxiety, aspiration penumonia, speech problems, feeding problems/FTT
167
what % of newborns are born w/ a major and minor anomaly?
3% - major
15% - minor
As number of minor anomalies ^ --> the risk of major anomaly ^
168
How is pyrexia a teratogen?
NTDs (affects neuralation)
169
What is maternal DM associated with in teratology?
Caudal dysgenesis, CHD, NTDs
170
what is smoking associated with in teratology?
CLP
IUGR
Preterm birth
171
What is toxoplasmosis infection associated with
Hydrocephalus and cerebral calcification
172
What does rubella cause in fetus?
cataract, deafness, PDA/pulmonary stenosis, CLP
173
Two ways you can get a teratoma?
1. aberrant PGC
| 2. Primitive streak persists
174
What Splits in meiosis I + II?
Meiosis I: homologous chromosomes
| Meiosis II: sister chromatids
175
What is the cause of turner's?
Non-dysjunction in spermatogenesis
176
when is nuchal translucency measured?
What about 1st trimester maternal blood serum screen?
11-14 weeks
10-14 weeks
177
What should nuccal translucency be less than?
3mm (if > then assoc. w/ CVS defects + T21...etc)
178
How does an anterior cleft palate form?
failure of lateral palatal process(es) to meet and fuse with primary palate
179
How does a posterior CP form?
failure of lateral palatal processes to meet and fuse with each other and nasal septum
180
What 4 reasons explain why a cleft palate happens?
Failure of normal growth of palatal shelves
Failure of fusion of palatal shelves
Obstruction of palate fusion by tongue
Failure of shelves to rise above tongue
181
When is a CP usually corrected?
1 year of age
182
How does a cleft lip form?
Unilateral = maxillary prominence fails to fuse with merged medial nasal prominences
Bilateral = failure of both maxillary prominences to fuse with the merged medial nasal prominences
183
When is a CL usually corrected?
3 months
184
Is CLP and CP found more in females or males?
CLP: Males
CP: females
185
What are the causes of CLP?
Syndromic
Related to genes but not syndromic
Non-syndromic: 70% CLP & 50% CPO
Teratogen exposure – SMOKING, anti-epileptics, benzos, RUBELLA
186
What are the features of DiGeorge syndrome?
CHD
Absent thymus + parathyroids (--> hypoparathyroid --> seizures)
low t-cell function
mild facial dysmorphology (shortened filtrum, low set ears, nasal cleft)
learning disability
187
What are the features of HPE?
Medial nasal prominences don’t form (due to deficient tissue)
Lateral nasal prominences fuse to form a proboscis with a single midline opening
Narrow head
Eyes fused
Upper lip formed by fusion of maxillary prominences
Single midline brain ventricle (fusion of lateral ventricles)
188
What are some causes of HPE/midline defects?
Alcohol
Maternal DM
SHH mutations
189
What is the TCOF1 gene associated with?
NCC differentiation
190
What is capacitation of the sperm?
Plasma proteins removed from cell membrane overlying the acrosome
191
What is the master heart gene?
NKX2.5
