Practical 1 - Gametogenesis Flashcards
What causes a teratoma? What is the most common location
Disruption to normal migration of primordial germ cells
Sacrococcygeal teratoma*
Oropharyngeal teratoma
What is a trisomy
additional chromosome to homologous pair (n=47)
What is a syndrome
Collection of symptoms assc with genetic abnormality
What is Edwards syndrome and what are the symptoms
Trisomy 18
- intellectual disability
- CHD
- Low set ears
- Flexion of fingers and hands
- Micrognathia
- Renal abnormalities
- Syndactyl &MSK malformations
What is the incidence of Edwards? How may make it to term?
1/5,000
35% lost by week 10 to term
Most live neonates die < 2 months
5% live beyond one year
What is Patau’s
Trisomy 13
- Intelectual disability
- Holoprosencephaly
- CHD
- Deafness
- Cleft lip and palate
- Anopthalmia
What is the incidence of Patau’s? How many survive?
1/20,000
90% dies within 1 month post natally
5% survive beyond 1 year
What is Klinefelters
47XXY - often due to nondisjunction of XX homologue
1/500
Found only in males, usually picked up on amniocentesis
- Sterile
- Testicular atrophy
- Hyalinazation of seminferous tubules
- Gynaecomastia
What is a barr body
inactive X chromosome in a female somatic cell, rendered inactive in a process called lyonization
What affects the phenotype after chromosome fragmentation
size of fragment
- if fragment lost - deletion
- if small amount lost - microdeletion
Fragile sites - tendency to break
What is Prader-Willi
Deletion of long arm chromosome paternal 15
(NB if maternal chromosome - Angelman’s (genomic imprinting)
- hypotonia
- obesity
- intellectual disability
- hypogonadism
- Undescended testis
What is a zygote
Single celled embryo
What is morula
16 celled embryo
what is a blastocyst
Occurs at time of implantation
Outer layer - trophoblast (contains fluid filled sphere)
Inner cell mass - embyroblast cells
Where does fertilisation usually occur?
Ampulla of the fallopian tube
How many days post fertilisation does implantation typically occur
8/9
Occurs in body of uterus
How do intra-uterine contraceptives work
IUD - release progesterone - prevents ovum release
Copper - irritates uterine wall
What is the incidence of ectopic pregnancy and what are the RF
2% (1.1% RCOG)
RF:
- Previous Hx
- Fallopian tube damage - previous surgery or infection
- Pregnancy w/ IUD or prog only pill
- IVF
- > 35 yrs
- Smoker
What are the signs and symptoms of ectopic
LOWER ABDOMINAL PAIN ECTOPIC UNTIL PROVEN OTHERWISE
Pallor - hypovolaemic shock
What is a lithopaediaon
Dead ectopic that becomes calcified
What is endometriosis
Ectopic endometrial tissue
6-10%
- dysmenorrhoea
- Dypareunia
- Pain on defaecation or micturition
- Menorrhagia
- Subfertility
NB irritation of peritoneum can cause adhesions and peritonitis
What structures can be affected by endometriosis
Ovaries Fallopian Tubes Tissues around uterus and ovaries Brain Lung
How do you manage endometriosis
Ablation
Progesterone contraception
How does endometriosis increase the risk of subfertility
Obstruction of the fallopian tube
May damage sperm or egg
Also increases risk of ectopic, reason unknown
What is the definition of subfertility
Failure to conceive after 1 year of trying
What are some male causes of sub fertility
CF
Aplastic vas deferens
Impotence
Decreased sperm count
What are some female causes of sub fertility
Fibroids
Abnormal shaped uterus
PCOS
Describe the development of the heart
Progenitor heart cells - derived from cranial end of primitive streak
Invaginate through primitive streak
Progenitor heart cells cluster on lateral plate mesoderm–> primary heart field (day 16-18)
PHF gives rise to atria, left ventricle, most of right ventricle
Primary heart fields are bilateral and will merge to form one cardiogenic tube
Secondary heart field appears (day 20-21) - gives rise to remainder of right ventricle and the outflow tract
(specifying laterality essential to ensure aorta arise from LV)
Cells are induced to form myoblasts and blood islands
Blood islands unite to form a tube surrounded by myoblasts (cardiogenic region)
Central part of tube expands - becomes bentricles and outflow tract
Heart tube formed in three layers (endo, myo, epicardium)
Heart tube elongates as cells added cranially from teh SHF - outflow tract elongation
Cardiac looping day 23-28
Major septa develop day 27-37 - formed by outgrowth of endocardial cushions
(interatrial, interventricular, AV valves and aortic and pulmonary channels)
Septum primum and then septum secundum separate atria
-f ovale normal foetal defect in this septum
During 5th work, common truncus divided by spiral septum, creating separate outflow tracts
NCC contribute lengthening of outflow tract and endocardial cushion formation
What is the difference between cyanotic and acyanotic CHD
Cyanotic
-R –> L shunt
Acyanotic
- L —> R
What is the function of the foramen ovale
Bypass the pulmonary circulation
If it remains patent –> Pulmonary HTN
What is an association of situs inversus
CHD
Primary ciliary dyskinesia
Why are SSRIs associated with laterality abnormalities
serotonin establishes left sidedness
What are some RF for CHD
Syndromes e.g. Edwards Genetic Rubella Thalidomide Accutane Alcohol
What is the incidence of ASD
- 4/10,000
2: 1 Female:Male
What is the incidence of VSD
12/10,000
80% occur in the muscular septum
What is the difference between muscular and membranous defects?
Membranous VSDs
- More serious defects
- Associated w/ abnormalities partitioning conotruncal regions e.g. teratology
What is Eisenmenger’s
Most commonly due to septal defect
Pulmonary resistance becomes so great that the shunt changes direction to R –> L i.e. right hypertrophy secondary to LR shunt
What is common truncus arteriosus
Conotruncal ridges fail to form
Defective interventricular septum
Pulmonary hypertension and bilateral ventricular hypertrophy
Associated with DiGeorge syndrome
Why might an infant with common truncus have craniofacial malformation
NCCs migrate to truncus
Defective NCC form outer of pharyngeal arches
What is transposition of the great vessels
Conotruncal septum fails to form spirally, runs straight down
Right sided aorta
Left sided pulmonary artery
What are the abnormalities associated w/ tetralogy of fallot
VSD
Pulmonary valve stenosis
LV hypertrophy
Overriding aorta
What are the symptoms of tetralogy
Cyanosis Dyspnoea Syncope Clubbing Poor weight gain Prolonged crying
What is coarctation
Narrowing of the descending aorta Infants: Pallor Dyspnoea Difficulty feeding
Left untreated may progress to fatal heart failure
When does gastrulation take place, what are the crucial events?
Formation of trilaminar disc in 3rd week
1) Invagination
- of primitive streak - cephalic end = primitve node
- epiblast invaginates
- cells migrate toward primitive streak
- movement controlled by FGF8
2) epiblast cells move through streak
- displace hypoblast, creating embryonic embyroderm and mesoderm
- cells remaining in epiblast –> ectoderm
Epiblast cells migrate to pass on each side of the pre-chordal plate - plate forms between tip of notochord and oropharyngeal mmbr
What is caudal dysgenesis, what are its symptoms, what are its associations
Insufficient mesoderm is formed in caudalmost region of embryo
This mesoderm contributes to formation of the lower limbs, urogenital system, lumbosacral vertebrae
Hypoplasia and fusion of lower limbs Vertebral abnormalities Renal agenesis Imperforate anus Anomalies of the genital organs
maternal diabetes
What is the vitelline duct
Communication between the midgut and the yolk sac
Define the formation of the gut tube
Lateral body walls will close to form the body wall, with only a communication to the yolk sac via the vitelline duct
What is the oropharyngeal membrane
ectodermal-endodermal membrane
Separates stomadeum (primitive oral cavity - ectoderm derived) from pharynx (endoderm derived)
Ruptures in the fourth week
What is the cloaca membrane
The hindgut temporarily terminates at ecto-endo mmbr
Separate upper anal canal from lower part (proctodeum)
Mmbr breaks in the 7th week
When are major organ systems formed
3rd to 8th week
- a critical period for normal development
- time when most gross structural defects are induced
- 3rd and 4th week particularly vulnerable
Stem cell populations are establishing the organ primordia, interactions sensitive to insult
When does the gut tube begin to form
3rd and 4th week
-same time as neurulation
What connects neural tube and gut tube
Mesoderm
- lateral plate components also splits into visceral and parietal layers
- visceral later rolls up and is intimately associated with gut tube
What is the paraxial mesoderm
Forms at the end of the third week from intraembyronic mesoderm
Forms somitomeres and somites
How is the diaphragm formed
Communication of pleural space and abdo via pericardia-peritoneal canal
Pleuroperitoneal folds appear beginning fifth week
Fuse with septum transversum and oesophagus mesentry (7th week)
How common are diaphragmatic hernias and what are the complications
1/2000
Due to failure of pleuroperitoneal mmbr to close the pericardioperitoneal canals
Peritoneal and pleural cavities are continous along the posterior body wall
Abdo viscera enter pleural cavity (85-90% left sided)
Push heart anteriorly and compress the lungs
Lungs may become hypoplastic
-high mortality (75%)
Where is a conceptus supposed to implant
anterior or posterior wall of uterine cavity
How does the mirena coil work
Thickens cervical mucus, preventing sperm entry
How does the copper coil work
Inhibits attachment of fertilised egg
Helps prevent passage of sperm
How do you investigate and manage a suspected ectopic
Urine pregnancy test
Transvaginal USS
Mx
- methotrexate
- Surgery - salpingectomy, saplingotomy
Why does endometriosis increase risk of subfertility and ectopic
Inflammation at site of ectopic endometrial tissue
Adhesions
What are some male causes of subfertility
CF Lack of vas deferens Impotence Decreased sperm count Varicocoele ED Anabolic
What are some female causes of subfertility
Fibroids Abnormal shaped uterus PCOS Endometriosis Ageing
Why does the foramen ovale close
Lungs inflate
Pulmonary resistance decreases
LA pressure increases
foramen ovale valve pressed against septum secundum
Foramen ovale obliterates –> Fossa ovalis
What symptoms may a ASD cause
Right side hypertrophy
Atrial fibrillation in older patient
Eisenmenger’s
Valve regurgitation
What is the result of a VSD
Dependent on size
Pulmonary ciculation can be 1.2 -1.7 x aorta due to LR shunt
Right sided hypertrophy –> heart failure
Pulmonary HTN –> Eisenmenger’s
What are the symptoms of tetralogy and its incidence
9.6/10,000 Cyanosis SOB FTT Syncope CLubbing Fatigue Heart murmur
Tet spells
-sudden cyanosis after crying, feeding, agitation
What complication may you get in coarctation
Dilated internal thoracic arteries
What is the incidence of coarctation
3.2/10,000
What is the distinction in coarctation
Preductal - PDA
Postductal - Obliteration of DA
what are the signs of post ductal coarctation
Right arm HTN
Decreased BP lower limbs
What is arhinencephaly
Failure of olfactory tract to form
Midline fused lateral ventricle
What are the key signalling factors for heart development
Signals from endoderm induces cells in primary heart field to form myoblasts
BMP2/4 upregulated
Endoderm blocks WNT protein synthesis (WNT proteins inhibit heart development)
Expression of BMP and inhibition of WNT allows expression of NKX2.5
(master gene for heart development)
What are the key molecules in establishing laterality
5HT
PITX2 expressed on left
(retinoic acid specifies caudal structures)
Situs invertus totalis incidence?
1/10,000
