Case 7 Flashcards
(214 cards)
1
Q
How long after ovulation can the oocyte be fertilised?
A
24hrs
2
Q
How long can sperm remain viable in female tract?
A
24hrs
3
Q
Capacitation
A
Removal of proteins by enzymes in plasma membrane of sperm.
Enables sperm to pass through coronal cells and undergo acrosome reaction.
4
Q
Acrosome reaction
A
Enzymes released from acrosome of sperm, which digest coronal cells. Allows sperm fuses with oocyte membrane.
5
Q
Where does fertilisation usually occur?
A
Ampullary region of uterine tube
6
Q
Cortical reaction
A
Formation of a fertilisation membrane after one sperm has entered.
Prevents triploidy.
7
Q
Cleavage
A
Rapid mitotic growth without growth.
8
Q
How does a morula differ from a blastocyst?
A
Blastocyst has formed an inner cavity.
9
Q
Inner cell mass will eventually become the..
A
Embryo
10
Q
Trophoblast eventually becomes the…
A
Placenta
11
Q
Blastocoele
A
Fluid filled space surrounded by trophoblast
Yolk sac
12
Q
Morula
A
Spherical 16-cell mass
4-7 days post fertilisation
13
Q
Blastocyst
A
Has a cavity inside the zona pellucida and an inner cell mass.
8-14 days post fertilisation
14
Q
Attachment of blastocyst to uterine epithelium
A
Blastocyst hatches from surrounding zona pellucida.
L selectin on trophoblast of blastcyst attaches to CHO receptors on endometrial wall.
15
Q
Function of syncytiotrophoblast
A
Invades endometrium causing spiral arteries to rupture
16
Q
Cytotrophoblast
A
Immediately surrounding embryo
17
Q
When does blastocyst reach the uterus?
A
6-7 days after fertilisation
18
Q
Apposition/Adplantation
A
Blastocyst is pressed against endometrium at the Inner Cell Mass region
19
Q
When is embryo completely surrounded by endometrium?
A
9-10 days after fertilisation
20
Q
Complete Implantation
A
Apposition - blastocyst becomes pressed against endometrium at ICM region.
Adhesion between L-selectins on trophoblast cells and CHO receptors on endometrial wall.
Syncytiotrophoblast secretes enzymes which break down endometrial cells.
21
Q
Decidual reaction
A
Stromal cells of uterine mucosa fill with glycogen.
Provides nourishment until placenta develops.
22
Q
Majority of abnormal implantations occur in…
A
Uterine tubes
23
Q
Placenta Previa
A
Low lying placenta.
Inserted into lower uterine segment.
Prevents natural birth.
24
Q
Placenta accreta
A
Abnormal invasion of endometrium and myometrium
25
Gastrulation
Conversion of bilayered blastula into an embryo with 3 layers
26
Primitive streak cells synthesise....
FGF8 - controls migration and specification.
27
Mechanism for gastrulation
Cells of epiblast migrate towards primitive streak, moving away from epiblast and slipping beneath it.
Invagination and lateral migration of epiblast cells.
28
Ectoderm derived tissues:
```
CNS
Pineal gland
Epidermis
Hair
Enamel
Inner ear
Retina and lens
```
29
Mesoderm derived tissues:
```
Cranium
Connective tissue
Urogenital system
Pericardium
Heart
Blood
Lymphatics
```
30
Endoderm derived tissues:
Epithelium of GI tract, respiratory tract, urinary bladder, parathyroid gland
31
Important proteins involved in neurulation
Wnt
| Shh
32
Wnt protein
Induces ecto and mesodermally derived tissues
33
Shh protein
Initially expressed in notochord.
Induces neural patterning.
Induces patterning of somites.
34
Neurulation
Cells in mesoderm just below primitive streak differentiate into notochord.
Induces formation of a thickening in ectoderm called the neural plate.
Neural plate cells dive into mesoderm and form a ring structure called the Neural Tube.
Neural tube formation induces cells from ectoderm to enter mesoderm - Neural crest cells.
35
Closure of neural tube occurs due to adhesion of which molecules:
E-cadherin
| N-cadherin
36
E-cadherin is found in...
External epidermis of skin
37
N-cadherin is found in...
Neural crest cells
38
Neuropores
Openings in neural tube
39
Neural tube closure travels from...
Neck region and continues posteriorly
40
Molecules responsible for dorsalisation of CNS
BMP and Wnt
41
Molecules responsible for ventralisation of CNS
Shh
42
Molecules responsible for caudalisation of CNS
Wnt and Retinoic acid
43
When does gastrulation occur?
Week 3
44
Neural Crest cells
Temporary group of cells found in mesoderm.
| Give rise to a number of different cells.
45
Neural Crest cells
Temporary group of cells found in mesoderm.
| Give rise to a number of different cells.
46
Cranial neural crest
```
Carilage and bone
Cranial neurons
Glia and CT of face
Bones of middle ear
Tooth primordia
```
47
Trunk neural crest
Dorsal root ganglia and sensory neurons
Sympathetic ganglia
Melanocytes
48
Vagal and sacral neural crest
Parasympathetic nerves of gut
49
Cardiac neural crest
Melanocytes
Neurons
Division between aorta and pulmonary artery.
50
Somites
Paired blocks of mesoderm. Arranged at either side of neural tube.
51
Somitogenesis
Formation of whorls of concentric mesoderm cells, producing pairs of identical somites which differentiate into the same cell types.
52
Hox (Homeotic genes)
Inform somites of their position.
53
Somites differentiate into...
Cartilage and bone
Muscles of ribcage, limbs and back
CT of dermis
54
Giemsa stain
Stains all parts of DNA equally, generating patterns of light and dark due to different amounts of coiling.
55
Telomerase
Recaps ends of chromosome which fray during replication.
56
Trisomy 21
Down's Syndrome
57
Why does nuchal translucency increase with Down's Syndrome?
Abnormal venous drainage
58
Physical features seen in infants with Down's Syndrome
```
Muscle hypotonia
Large tongue
Brushfield spots (white spots in iris)
Single palmar crease
Flattened nose
Curved 5th finger
Sandal gap deformity
Low set ears
Epicanthal folds
```
59
Features of Down's Syndrome in later life
Developmental delay
| Obesity
60
People with Down's Syndrome are at an increased risk of...
```
Heart disease
Thyroid disorders
Conductive hearing loss
Immune dysfunction
Leukaemia
Seizures (15%)
Dementia (75% by 65yrs)
```
61
Trisomy 18
Edward's Syndrome
62
Prognosis for Edwards syndrome
75% miscarried or stillborn
| 5-10% survive to 1 year
63
Common features of Edward's Syndrome
```
Arthrogryposis (joint contractures)
Rocker bottom foot with prominent calcaneus
Clenched hands with index and 5th fingers overriding 3rd and 4th
Skeletal defects
Cleft lip/palate
Heart and urogenital abnormality
Seizures
Developmental delay
```
64
Trisomy 13
Patau Syndrome
65
Prognosis for Patau Syndrome
20% survival at 1 year
66
Common features of Patau syndrome
```
Microcephaly
Holoprosencephaly (failure of forebrain division)
Cleft palate
Cutis Aplasia (missing skin, usually scalp)
Craniofacial defects
Polydactyly
Omphalocoele
Urogenital and heart defects
Seizures
Developmental delay
```
67
Holoprosencephaly
Failure of forebrain division and midline formation.
| Seen in Patau syndrome
68
Cutis Aplasia
Missing skin, usually on scalp, seen in Patau syndrome
69
Hypotelorism
Short distance between eyes, seen in Patau syndrome
70
Cyclopia
One eye
| Seen in Patau syndrome
71
Proboscis
Tube rather than a nose
| Seen in Patau syndrome
72
Polydactyly
Many fingers
| Seen in Patau syndrome
73
Omphalocoele
Liver and intestines outside the body.
| Seen in Patau syndrome
74
Mosaicism
When someone is composed of cells of 2 genetically different types.
Caused by errors in post-zygotic mitosis e.g. non dysjunction and trisomy rescue
75
Germline mosaicism
Mutated cells only found in testis or ovaries.
| Asymptomatic but offspring may be affected.
76
Possible triploidies
69 XXX
69 XXY
69 XYY
77
Diandry
Egg fertilised by 2 sperm or a diploid sperm
| Accounts for 60-80% of triploidy cases
78
Effect of diandry
Large placenta
| Small foetus
79
Digyny
Diploid egg fertilised by 1 sperm
| 20-40% of cases
80
Effect of Digyny
Small placenta
| Very small foetus
81
Features of troploidy
```
Misscarriage/Stillbirth
Early neonatal death
Prematurity
Craniofacial dysmorphism
Hypotonia
Eye/gut/brain/cardiac/limb/GU abnormalities
```
82
Why are sex chromosome aneuploidies more mild?
Y chromosome is small and X chromosome can be inactivated
83
Barr body
Condensed, inactive X chromosome
84
47XXY
Klinefelter syndrome
85
Features of Klinefelter Syndrome
```
Hypogonadism and infertility
Gynaecomastia
Absent secondary sexual characteristics
Small testes
Tall stature
Shy and apprehensive
```
86
People with Klinefelter syndrome are at higher risk of...
Female associated health problems e.g. Breast cancer, thyroid problems
87
Management of Klinefelter syndrome
Testosterone and fertility treatment
| Treat gynaecomastia
88
Features of 47 XYY syndrome
Normal intelligence, testosterone and fertility.
Tall
Aggressive/antisocial
Severe acne
89
45X
Turner Syndrome
90
Visible features of Turner Syndrome
Neck webbing
Broad, flat chest with widely spaced nipples
Low set ears
Increased carrying angle of elbows
91
Sexual characteristics of Turner Syndrome
Streak ovaries
Lack of sexual development
Primary amenorrhoea
Infertile
92
Physiological characteristics of Turner Syndrome
Heart and kidney defects
Increased risk of IBD
Hypothyroidism
93
Management of Turner Syndrome
GH in childhood
Oestrogen in adolescence
Surgery for webbing
IVF/Egg donation
94
Risks of balanced reciprocal translocation
Infertility
| Recurrent miscarriage
95
Ring chromosome
A chromosome whos arms have fused together to form a ring
96
Ring chromosome 20
Associated with Seizures
97
Robertsonian Translocations most commonly occur between..
Chromosome 13 and 14
98
45,XX,der(13:14)
Robertsonian Translocation between chromosome 13 and 14.
| Combination of small arms of 13 and 14 have been lost.
99
Uniparental Disomy
2 copies of a chromosome come from the same parent.
| May occur due to trisomy rescue (deletion of a third chromosome)
100
Risk of Down's syndrome when mother carries the Robertsonian Translocation
10%
High risk as there is no competition between eggs.
101
Risk of Down's Syndrome when father carries the Robertsonian translocation
<0.5%
Low risk since abnormal sperm are outcompeted
102
5p Deletion (deletion of short arm of chromosome 5)
Cri Du Chat
103
Interstitial Deletion 15q11-q13
Prader-Willi Syndrome
| Angelman Syndrome
104
Features of Prader-WIlli Syndrome in the newborn
Weak feeding, hypotonia, slow development
105
Features of Prader-Willi Syndrome in a child
```
Constantly hungry
Obesity (+diabetes)
Narrow forehead
Small hands and feet
Short
Intellectual and behavioural problems
Hypogonadism
```
106
Features of Angelman Syndrome
```
Delayed development and intellectual disability
Severe speech impairment
Gait ataxia
Epilepsy
Microcephaly
Excitable/Hyperactive
Fair coloured skin and hair
Scoliosis
```
107
Intersitial deletion 22q11.2
DiGeorge Syndrome
108
Inheritance pattern for DiGeorge Syndrome
Autosomal dominant
109
Features of DiGeorge Syndrome
```
Heart abnormalities (74%)
Palate abnormalities (69%)
Immun deficiencies (77%)
Hypocalcaemia (50%)
Learning disabilities (70-90%)
```
110
Use of Fluorescent In Situ Hybridisation (FISH)
For small changes in genes, too small to be seen by karyotyping (e.g. microdeletion 22q11.2)
111
Micro Array-Based Comparative Genomic Hybridisation
Detects changes in genes and chromosomes.
| Used in most post and prenatal cytogenetic testing.
112
Problems with Array-CGH
Incidental findings e.g. Huntington's
113
Malformations usually occur at what stage of gestation?
3-8wks
114
Disruptions
Alterations of pre existing structures due to destructive forces e.g. Amniotic band syndrome
115
Amniotic band syndrome
```
Foetus entangled in amniotic bands
Decreased blood flow causing:
Club hands
Cleft lip/palate
Syndactyly
Amputation
```
116
Deformations are caused by...
Mechanical factors
117
Syndrome
Pattern of malformations occurring together that are thought to have a specific common cause
118
Teratogens
Disrupt embryonic or foetal development during critical periods.
Produce malformations/birth defects
119
Fragile X Syndrome
Fragile sites found in regions of CCG repeats.
| Causes mental retardation, large ears, prominent jaw and autism
120
Effect of chemical agents during 1st trimester
Congenital malformations
121
Effect of chemical agents during 2nd/3rd trimester
Affect foetal growth and functional development
122
Effect of chemical agents near term/during labour
Adverse affects on labour and neonate after birth
123
Effect of thalidomide on foetus
Missing limbs
Facial, CV and CNS abnormalities
Increased risk of prematurity and spontaneous abortion
124
Effect of Isotretinoin (Analogue of Vit A used for acne) on foetus
Facial abnormalities
Low IQ
CNS and CV problems
125
Effect of Rubella infection during first trimester
Congenital Rubella Syndrome
Cataracts
Cardiac defects
Deafness
Mental retardation
126
Effect of rubella infection during weeks 13-16 gestation(Early 2nd trimester)
15% have deafness and retinopathy
127
Effect of Rubella infection after 16 weeks gestation
Normal development
SMALL risk of deafness and retinopathy
128
Why does alcohol intake by a pregnant woman have a detrimental effect on the foetus?
Foetal liver does not have alcohol or aldehyde dehydrogenase
129
Effect of alcohol intake during 1st trimester
Foetal Facial deformity
```
Smooth Philtrum
Abnormal ear cartilage
Wide set eyes/Epicanthal folds
Small upper lip
Microcephaly
```
130
Effect of alcohol intake during 2nd trimester
Increased risk of spontaneous abortion
131
Effect of alcohol intake during 3rd trimester
Effect weight, length and brain growth of baby.
132
Facial deformity seen in Foetal Alcohol Spectrum Disorders
```
Smooth Philtrum
Abnormal ear cartilage
Wide set eyes/Epicanthal folds
Small upper lip
Microcephaly
```
133
Effect of smoking during pregnancy
IUGR
2x more likely for premature delivery
Low birth weight (<5lb)
134
Why does smoking affect pregnancy?
Nicotine constricts blood vessels - reducing blood supply to foetus.
Nicotine can cross blood:placenta barrier - affects brain development and impairs cell growth
135
Effect of hyperthermia in pregnancy
```
Neural tube defects
Micropthalmia (small eyes)
Cataracts
Microencephaly
Craniofacial defects (clefts)
Behavioural problems
```
136
Effect of cocaine use during pregnancy
Spontaneous miscarriage
Premature labour
Difficult delivery
Low birth weight and small head circumference
137
What screening do we carry out for pregnant women in Wales?
Hep B
Sickle cell anaemia + thalassaemia
Down's Syndrome (NT)
Blood group + Ab
138
Features of trinucleotide repeat disorders
Symptoms of disorder become more severe/have an early onset with each generation
139
Trinucleotide repeat disorders
Myotonic Dystrophy
Huntington's Disease
Fragile X Syndrome
140
Inheritance pattern for Myotonic Dystrophy
Autosomal Dominant
141
Inheritance pattern for Huntington's Disease
Autosomal Dominant
142
Inheritance pattern for Fragile X Syndrome
X linked Dominant
143
Features Myotonic Dystrophy
```
Progressive muscle wasting and weakness
Slurred speech
Myotonia (unable to relax muscles after use e.g. Jaw locking)
Cataracts
Cardiac conduction defects
```
144
Breast cancer susceptibility genes
BRCA1 (20-30%)
| BRCA2 (10-20%)
145
Phenocopy
Individual without the specific gene gets the condition
146
Non penetrance
Individual with the specific gene does not get the condition
147
Sex limitation
Male with specific gene for a condition only affecting females, does not get the condition
148
Variable expression
Example
| Female with gene for breast cancer gets ovarian cancer
149
Hardy-Weinberg Equation
p2 + 2pq + q2 = 1
Where p+q=1
150
Somatic mosaicism
Some cells lack the mutation, therefore a more mild phenotype is expressed
151
Constitutional mutation
Inherited from a gamete (germline mutation) or occurs soon after fertilisation
152
Chimerism
One organism composed of 2 or more populations of genetically distinct cells, originating from different zygotes
153
Chimeric Singleton
Where one twin dies and becomes integrated with the other foetus
154
Therapeutic chimerism
Haemopoietic stem cell treatment
155
Placental anastomoses
Occurs in 8% of dizygotic twins. Gives rise to chimerism
156
Epigenetics
Changes in organisms caused by modification of gene expression rather than an alteration of the genetic code itself
157
Genetic Imprinting
Gene expression which depends on which parent the gene was inherited from.
Occurs as a result of epigenetics.
158
Maternal inheritance of 15q11-q13
Angelman Syndrome
159
Paternal inheritance of 15q11-q13
Prader Willi Syndrome
160
Why is folic acid given in pregnancy?
Reduces incidence of neural tube defects e.g. spina bifida, acrania, anencephaly
161
Folic acid treatment before/during pregnancy:
400 micrograms when trying to conceive and during first 12 weeks of pregnancy.
5mg for women at high risk (Hx of NTD or family Hx)
162
Haemolytic disease of newborn
Anaemia
Hyperbilirubinaemia
Kernicterus (bilirubin induced neurological deficit)
163
Prevention of Rhesus Disease
Anti-Rh given to rhesus positive mothers after birth and at sensitisation events (e.g. car accident)
164
Combined Test consists of:
US measurement of CRL and NT
| Biochemical markers: beta hCG in blood and pregnancy associated plasma protein A
165
When must combined test be carried out?
10-14wks gestation
166
When is combined test less accurate?
Obese women
167
Quadruple test consists of:
US measurements of CRL and head circumference
Biochemical markers:
Foetal serum albumin (AFP), hCG, unconjugated estradiol (uE3) and inhibin A
168
Quadruple test results which would suggest high risk pregnancy
High AFP = neural tube defect
High hCG = T21
Low uE3 = T21
169
When is quadruple test indicated?
When time frame for Combined test is missed
| Women with BMI > 40
170
Time frame for Quadruple Test
14-20wks gestation
171
What happens if QT/CT gives a high risk result?
Mother is offered diagnostic tests - CVS or amniocentesis
172
At what stage in gestation can CVS be carried out?
After 11 weeks
173
Risks of CVS
>1% risk of miscarriage
| Up to 5% of tests do not give a result
174
Chorionic Villus Sampling
Aspitation of chorionic villi through abdomen under US guidance
175
Amniocentesis
Aspiration of amniotic fluid
176
Risks of amniocentesis
1% risk of miscarriage
1% risk of infection
1% of tests do not give a result
177
At what stage in gestation can Amniocentesis be carried out?
After 15 weeks
178
What is the disadvantage of amniocentesis?
Takes place late in pregnancy.
If a termination is requested, treatment is:
Foeticide - injection of KCl into foetal heart
179
When is screening for Syphilis, Hep B and HIV carried out for a pregnant woman?
8-12 weeks
| Can be at any time
180
When is screening for Sickle Cell Anaemia and Thalassaemia carried out for a pregnant woman?
0-10weeks
181
When is screening for blood group and rhesus disease carried out for a pregnant woman?
8-10 weeks
| Can be at any time
182
NIFTY/NIPT
Diagnostic test examining maternal blood.
Low risk
Can be carried out on twin pregnancies (only give result for one foetus)
183
CVS and Amniocentesis do not give an accurate result for...
Twin/Multiple pregnancies - since there is already a higher risk of miscarriage
184
Features of Autosomal Dominant Inheritance
Multiple generations
Males and females affected equally
Incomplete penetrance i.e. unaffected carriers
185
Conditions with Autosomal Dominant Inheritance patterns
```
Huntington's
FAP
Familial Hypercholesterolaemia
LQT
Myotonic dystrophy
Hereditary breast.ovarian cancer
Marfan's Syndrome
```
186
Features of Autosomal Recessive Inheritance
Usually only one generation affected
Often childhood onset
Common in consanguinous families
187
Conditions with Autosomal Recessive Inheritance patterns
```
B-Thalassaemia
Sickle Cell
Phenylketonuria
Tay Sachs
Spinal Muscular Atrophy
MYH Associated Polyposis
```
188
Recurrence risk after a couple has one child affected with an AR condition
25%
189
Features of X-Linked Recessive inheritance
Usually only affects males
Affected males can never transmit condition to their sons.
Daughters of affected males are always carriers
190
Examples of X-Linked Recessive conditions
Duchenne Muscular Dystrophy
Haemophilia A
Red-Green colour blindness
191
Penetrance
Frequency with which the characteristic controlled by a gene is seen in individuals possessing it
192
Pseudodominant
Where a recessive condition appears to transmit dominantly.
| Usually occurs in consanguinous families
193
Features of X-linked dominant inheritance
Higher incidence in females
Affected male gives condition to all daughters and not to sons.
Affected female gives condition to half of her sons and half of her daughters
194
Examples of X-linked Dominant conditions
Vitamin D resistant rickets (hypophosphataemic)
Rett's Syndrome
Fragile X syndrome
195
Incontinentia Pigmenti
X linked dominant.
| Males die in utero. Females inactivate a chromosome and survive
196
Features of Incontinentia Pigmenti
```
Blistering (0-4 months)
Wart like rash and hypopigmentation
Alopecia
Hypodontia (missing teeth)
Dystrophic nails
Retinal detachment
Developmental delay/learning disability
```
197
Features of Y linked inheritance
Males only
| Often affects fertility - unlikely to be passed on
198
Features of mitochondrial inheritance
Transmitted mother to child only
199
Examples of mitochondrial inherited conditions
Leber Hereditary optic neuropathy
Chronic progressive external opthalmoplegia
200
Leber Hereditary optic neuropathy
Sudden permanent vision loss due to optic atrophy in young adult
Mitochondrial inheritance
Low penetrance - only 50% of male carriers are symptomatic, only 15% of female carriers are symptomatic
201
Chronic progressive external opthalmalgia
Weakness of muscles of the eye
Loss of function of eye and eyelid movement.
Mitochondrial inheritance
202
Why does imprinting affect foetal growth?
Paternal genome wants to maximise resources for foetus.
| Maternal genome wants to minimise resources for foetus.
203
Bechwith-Wiedmann Syndrome
Paternally inherited 11p15 mutation (imprinting)
```
Macroglossia
Neonatal hyperinsulinism (large pancreas)
Large limbs and body
Wine stained skin
Ear creases
Increased risk of cancer
```
204
Silver Russell Syndrome
Maternally inherited 11p15 mutation (imprinting)
```
Small
Feeding problems
Hypoglycaemia
Clinodactyly
Hypospadias
```
205
Clinodactyly
Curved little finger (outward curvature)
206
Hypospadias
Urethral opening is in an abnormal position
207
Why is ibuprogen contraindicated in pregnancy?
Causes neonatal haemorrhage due to thrombocytopenia
208
Fundal height at 12 weeks gestation
Pubic symphysis
209
Fundal height at 20wks gestastion
Umbilicus
210
Fundal height at 36wks gestation
Xiphoid process of sternum
211
Quadruple test results suggesting high risk of Down Syndrome
High hCG and Inhibin A
| Low AFP and Estriol
212
Protein responsible for dorsalisation of CNS
Wnt and BMP
213
Proteins responsible for caudalisation of CNS
Wnt and Retinoic acid
214
Proteins responsible for ventralisation of CNS
Shh
