Theme 2 - Reproductive system, fetal development and birth Flashcards
8 effects of testosterone
Increased aggression and libido* Enlargement of the larynx Male pattern pubic hair Maturation of genitalia Muscle development Sperm production Bone growth* Acne
8 effects of oestrogen and progesterone
Bone Growth Female psyche Fair complexion Breast Development Widening of the pelvis Maturation of genitalia Female pattern pubic hair Subcutaneous fat deposition
Draw a graph to show changes in hormone levels throughout menstrual cycle
Start on day of bleeding Increase oestrogen and FSH Drop in FSH then oestrogen LH surge (ovulation) Increase in progesterone and oestrogen then both drop off
What acts of legislation governs conscientious objections and regarding reproduction and fertility what are the key points?
Abortion Act 1967
Human Fertilisation and Embryology Act 1990
no person shall be under any duty, whether by contract or by any statutory or other legal requirement, to participate in any treatment authorised by this Act to which he has a conscientious objection
Nothing in subsection (1) of this section shall affect any duty to participate in treatment which is necessary to save the life or to prevent grave permanent injury to the physical or mental health of a pregnant woman
What is the time limit on embryo research, and why?
14 days – before possibility of twinning. Justification is that prior to this stage, the embryo isn’t part of a continuum for an identifiable future person.
What is the Warnock position on moral importance and at what stage of development?
there is no particular part of the developmental process that is more important than another; all are part of a continuous process
What 3 things to female oral contraceptives do to prevent conception?
Prevent ovulation
Thicken cervical mucus
Hostile endometrium
What effect does the progesterone only contraceptive pill have on the menstrual cycle and how does it prevent conception?
inhibit ovulation by suppression of LH surge, thicken cervical mucus and render the endometrium ‘hostile’.
3 examples of progesterone only contraceptive
norethisterone, levonorgestrel, desogestrel
Adverse affects of progesterone only oral contraception (up to 7)
Menstrual irregularity, nausea, vomiting, headache. Breast discomfort, weight changes, changes in libido.
Potential male contraceptive hormone mechanism of action?
Injection of testosterone agonist to generate negative feedback and progesterone to suppress LH. The aim is to halt spermatogenesis.
Adverse affects of male hormone contraception
The most common adverse events were acne, injection site pain, increased libido, and mood disorders
What 2 types of neuron stimulate GnRH
Kisspeptin and the KNDy
What des FSH act upon and what does this produce?
Primary follicle in granulosa cells
To produce oestrogen and inhibin
FSH leads to an increase of what type of receptor in the graulosa cells?
LH
Oestrogen and inhibin usually inhibit FSH by negative feedback, but when is this not the case and what does this cause?
When oestrogen reaches critically high levels they positively act on the Kisspeptin and KNDy neurones which stimulate the production of GnRH which in turn produces LH (due to increased frequency and amplitude of the pulse from GnRH). Triggers ovulation
How can ovulation be diagnosed?
Day 21 progesterone blood test
Urinary LH detection kit
Trans vaginal pelvic ultrasound
Causes of ovulation problems in the hypothalamus?
Hypothalamus (lack of GnRH)
- Kiss1 gene deficiency- rare
- GnRH gene deficiency - rare
- weight loss/stress related/excessive exercise
- anorexia/bulimia
Causes of ovulation problems in the pituitary?
Pituitary (lack of FSH and LH)
- pituitary tumours (prolactinoma/other tumours)
- post pituitary surgery /radiotherapy
Causes of ovulation problems in the ovary?
Ovary (lack of oestrogen/progesterone)
- Premature ovarian insufficiency
- Developmental or genetic causes eg Turner’s syndrome
- Autoimmune damage and destruction of ovaries
- Cytotoxic and radiotherapy
- Surgery
Polycystic Ovarian Syndrome: commonest cause
Amenorrhoea definition
lack of period for more than 6 months. Primary - never. Secondary -have stopped.
Oligomenorrhoea definition
irregular periods. Usually occurring more than 6 weeks apart.
Polymenorrhoea definition
periods occurring less than 3 weeks apart
Hirsuitism definition
Androgen dependent - in male distribution
3 Clinical features of PCOS
Hyperandrogenism -Hirsutism, acne Chronic oligomenorrhoea / amenorrhoea - 9 periods / year -Subfertility Obesity (but 25% of women with PCOS are “lean”)
How does PCOS affect LH and FSH levels?
Exaggerated pulsatile release of GnRH causes an increase of circulating LH an an increase in the ratio of LH:FSH.
How does the increase in LH:FSH ratio in PCOS affect androgen levels?
Ovarian theca cells respond to LH by increasing conversion of cholesterol to androgen. The realtive lack of FSH prevents this from being converted to oestrogen.
How does hyperandrogenism in PCOS account for its associated symptoms?
Increased androgen causes local follicular arrest and therefore amenorrhea/oligoamenorrhea.
Stimulation of sex-responsive hair follicles causes hirsuitism and acne.
What happens to insulin resistance in pats with PCOS?
Insulin resistance increases
How does insulin resistance in pts with PCOS relate to hyperandrogenism?
Insulin synergises with LH to increase androgen production by theca cells.
Inhibits hepatic production of SHBG and therefore increases the amount of free androgen.
Are the cysts in PCOS?
Actually small follicles
What are the effects of testosterone and oestrogen on SHBG?
SHBG increased by oestrogens
SHBG decreased by testosterone thus releasing more free testosterone
What is the most common cause of anovulation?
PCOS
What are the 3 reproductive affects of PCOS?
Reduction in fertility (to a varying degree)
Increased risk if miscarriage
Increased risk of gestational diabetes
How does PCOS relate to risk of endometrial cancer and why?
Increased risk due to the lack of progesterone.
Endometrial cancer also associated with T2 diabetes and obesity
Best treatment for PCOS
Lifestyle modification - diet and exercise
How would the COCP help treat PCOS? (3)
increases SHBG and thus decreases free testosterone
decreases FSH & LH and therefore ovarian stimulation
regulates cycle & decreases endometrial hyperplasia
What are the risks with using the COCP to help treat PCOS?
Increase weight gain may exacerbate metabolic sydrome
What medication could be used in combination with the COCP to treat PCOS? 2 examples
Anti androges
-Spironolactone - anti mineralocorticoid and anti androgen properties
-Cyproterone Acetate (oral tablet)
inhibits binding of testosterone & 5 alpha dihydrotestosterone to androgen receptors
What drug could be used to help treat the insulin resistance in women with PCOS?
Metformin
Definition of Premature ovarian failure/primary ovarian insufficiency
Cessation of menses before age 40 in absence of genetic abnormalities.
How may POF/POI present?
Primary or secondary amenorrhea . Possibly with hot flashes.
Aetiology of POF/POI?
Autoimmune
Iatrogenic - surgery/radiotherapy
Genetic - Turners syndrome
Genetic predisposition
What is Turner’s syndrome?
Absence of second sex chromosome
XO 50%
rest mosaicism or partial
How may Turner’s syndrome present?
Women Primary/secondary amenorrhea Short stature webbed neck shield chest
Conditions associated with Turner’s?
CV system -Coarctation of aorta -Aortic dissection -Hypertension (adults) Renal Congenital abnormalities Metabolic syndrome Hypothyroidism Ears / hearing problems
Most common causes of hirsuitism?
PCOS or idiopathic hirsuitism (95%)
When would hirsuitism be a cause for concern?
Sudden onset of severe symptoms Virilisation Frontal balding Deepening of voice Male-type muscle mass Clitoromegaly Possible Cushing’s syndrome
Least common causes of hirsuitism?
Cushings
Ovarian tumor
Non-classical congenital adrenal hyperplasia (CAH)
What is the causes the majority (95%) of cases of congenital adrenal hyperplasia?
21-hydroxylase deficiency
How will CAH present in children and what type of CAH is this known as?
Classic/severe -Salt wasting Hypovolaemia, shock -Virilisation Ambiguous genitalia in girls Early virilisation in boys Precocious puberty -Abnormal growth Accelerated early Premature fusion
How will CAH present in adults and what type of CAH is this known as?
non-classic/mild Hirsutism Oligo / amenorrhoea Acne Subfertility
Similar to ‘PCOS’ presentation
Where in the testes does spermatogenesis occur?
seminiferous tubules
Which cells produce testosterone?
Leydig cells
Following production in the Leydig cells, where is testosterone distributed to? 3
majority into blood stream
some into lymphatic system
some into the Sertoli cells within seminiferous tubules to facilitate spermatogeneis
What cells in the testes are stimulated by LH and what is the affect of this?
Leydig cells - to produce androgen
What cells in the testes are stimulated by FSH and what is the affect of this?
Sertoli cells - for spermatogenesis
What are the 3 elements of spermatogenesis?
Mitotic proliferation to produce lots of cells
Meiotic division to generate genetic diversity
Cell modelling to package chromosomes for delivery to the oocyte
In what part of the semiferous tubule does mitosis od the prospermatogonia occur?
Basal
What is the name of the cells that emerge from the first round of mitosis during spermatogenesis?
A1 spermatogonia
What is the name of the cells that emerge from the final round of mitosis during spermatogenesis?
primary spermatocytes
Where does meiosis of sperm primary spermatocytes take place?
adluminal compartment
What is the name of the cells that emerge from the first division of mieosis during spermatogenesis?
Secondary spermatocytes
What is the name of the cells that emerge from the second division of mieosis during spermatogenesis?
spermatid
Draw and label a sperm - 5 points
5: Tail for forward propulsion
4: Midpiece with mitochondria for energy
3: Nucleus with packaged chromosomes
2: Cap region forms for sperm-oocyte fusion
1: Acrosome
What is the interval between subsequent sperm production?
16 days
Time for completion of spermatogenesis?
64 days
What’s in jiz and whats the point of it? 4 points
Nutrition (fructose, sorbitol)
Buffer (to protect against vaginal acidity)
Antioxidants (ascorbic acid, hypotaurine
In the endocervix, what hormones make the mucus watery/inhibit secretory activity?
Oestrogen - watery
Porgesterone - inhibit production
From what day in the cycle can sperm penetrate the mucus?
day 9
where does sperm capacitation take place?
endocervix
What is capicatation?
Stripping of glycoprotein from sperm surface which accumulates in the epididymis
Causes hyperactive motility – ‘whiplash’
What are the 3 properties of cervical mucus?
Consistency (watery or viscous)
Spinnbarkeit (means elasticity, stickiness)
Ferning (crystalisation on a glass surface)
Normal ejaculated sperm volume
1.5 -6ml
What 5 variables are assessed in a jiz sample?
Volume Concentration Vitality Motility Morphology
What 2 factors determine what indifferent gonads become?
hormones
genetic switches
In female development what duct is kept and why?
Mullerian due to absence of AMH
In male development what duct i kept?
Wolffian due to AMH getting rid of Mullirian
In males, what hormone stimulates the development of the urethra, prostate and external genitals?
dihydrotestosterone
In males and females what do the following develop into? Genital tubercle Urethral folds Labialscrotal swellings Urethral groove
Men: Penis fuse to become spongy urethra scrotum n/a Women; clitoris labia minora labia majora vestibule
What is true hermaphroditism in terms of internal and external genitalia as well as karyotype?
Both ovaries and testes present
external can appear male or female
46XX (SRY+), 45X (SRY+) and 45X
What is female psuedohermaphroditism in terms of internal and external genitalia as well as karyotype?
Internal sex organs normal
labia may be fused with enlarged clitoris
46, XX with virilization (due to androgens)
What is male psuedohermaphroditism in terms of internal and external genitalia as well as karyotype?
External genitals: incompletely formed, ambiguous or clearly female
Testis: normal, malformed or absent
46, XY with undervirilization
2 possible causes of male psuedohermaphroditism
Androgen Insensitivity Syndrome (AIS)
-Hormone secreted but receptors defective
Leydig Cell Hypoplasia
- Leydig cells do not secrete testosterone
What 5 things is the 10-14 week pregnancy scan looking for?
Viability Accurate dating Detecting multiple pregnancy Detecting structural abnormalities Screen for chromosomal conditions
What 4 structural abnormalities can be detected at the 10 - 14 week scan?
spina bifida
anencephaly
exomphalos & gastroschisis
bladder outflow obstruction
At what stage of pregnancy is combined screening given?
11-14 weeks
What is the combined test screening for?
Trisomy 21, 18 and 13
What are the three components of the combined test?
Maternal age
Nuchal Translucency
Serum niomarkers PAPPA/beta-hCG
What influencing factors are there for combined screening? 9 points
Maternal age Gestational age Ethnicity Smoking IVF Multiple pregnancy Weight Diabetes Past history of chromosome abnormality
Follwing combined screening, what is the cut off between low/high risk?
1 in 150
When does the quadruple test take plce and eehat does it screen for?
14-20 weeks. Trisomy 21
How does Non Invasive prenatal Testing Work?
Cell free foetal DNA in maternal bloodstream (from 10 weeks) can be tested.
What is the difference between monozygous and dizygous twins and what proportion of twin births does each account for?
mono -1 egg. Identical twins. 1/3 of twin births
di - 2 eggs. non identical 2/3 of births
Explain how both monozygotic and dizzygotic twins can be dichorion diamnion?
If monozygotic and splitting occurs very early, within 24 hours. Then separate chorion, amnions and placenta will form
If splitting occurs in blastocyst at around 4 days from monozygous twin what will this likely result in?
Monochorion diamnion
If the splitting occurs later than the blastocyst stage in a monzygous twin what will this result in?
Mono chorion, mono amnion
How can twin pregnancy be diagnosed? 3 points
Uterine size
at delivery
ultrasound
Definitions for: Stillbirth early neonatal neonatal perinatal infant
24 weeks first 7 days 28 days SB - early neonatal first year (rates per 1000)
What is twin to twin transfusion syndrome?
Unbalanced placental anastamoses. Resulting in a unidirectional AV shunt. One twin becomes the donor the other the recipient.
At what stage of pregnancy are twins delivered?
DC twins 37-38 weeks
MC 36-37 weeks
Two options for surgical abortion?
Vacuum aspiration (under 14 weeks) Dilation and extraction (over 14 weeks, rare)
Medications for abortion and how they work?
Mifeprestone - progesterone antagonist takenorally that stops the pregnancy
Misoprostal - E1 analogue induces labour
Where in the Fallopian tube does fertilisation usually occur?
Ampulla
Order and timings of: blastocyst, morula, zygote
Zygote - fertilisation
Morula - 72 hours
Blastocyst - 4 days
What happens in days 4-5 of fetal development? 3 points
Morula forms cavity and becomes blastocyst.
part of the blastocyst thins out and becomes the trophoblast.
Rest of the cell mas moves up to from the embryonic pole.
What happens in day 6 -7 of fetal development? 2 points
Inner cell mass differentiates into 2 cell layers - epiblast and hypoblast?
What do the epiblast and hypoblast go onto form?
Epiblast - embryo ans amnion
Hypoblast - yolk sack
From days 16+ of fetal development what do the following become:
Epiblast
Hypoblast
Epiblast - becomes ectoderm, endodrem and mesoderm
Hypoblast - degenerates
in placental development, what burrows into the myometrium?
Syncytiotrophoblast
In fetal development, what do the following do/become? Syncytiotrophoblast Cytotrophoblast lacunae mesoderm
Syncytiotrophoblast invades decidua (endometrium)
Cytotrophoblast cells erodes maternal spiral arteries and veins
Spaces (lacunae) between the fill up with maternal blood
Followed by mesoderm that develops into fetal vessels
What hormones does the placenta produce aand what do these do? 2 points
Human chorionic gonadotrophin (HCG)
- maintaones corpus luteum in pregnancy
Human placental lactogen HPL
- growth, lactation
- carbohydrate and lipid
What can transfer can cross the placenta and how? 4 points
Gases – oxygen and carbon dioxide by simple diffusion
Water and electrolytes
Steroid hormones
Proteins poor – only by pinocytosis
At what point are maternal antibodies transferred across the placenta?
from 12 weeks but mainly after 34
What is the capsularis, basalis and parietalis?
capsularis - capsule overlying embryo and chorionic cavity
parietalis - pert of uterus not occupies by embryo
basalis - between uterine wall and chorionic villi
What is vasa ts consequences and treatment??
Umbilical cord lies over the the cerivical os. Massive bleeding. Detect via ultrasound, caesarian section
What is placenta accreta, its consequences and treatment?
failure of placenta to separate at birth. Massive bleeding. Hysterectomy
What is placenta praevia its consequences and treatment?
Placenta overlies cervical os. Massive painless bleeding. C section
What is placental abruption its consequences and treatment?
Detachment of placenta during pregnancy. massive painful bleeding (possibly concealed).
At what stage of gestation does fetal growth vs development take place?
12 weeks. before this mainly about organ growth.
What 2 types of growth problems are there?
Small for gestational age
Intrauterine growth restriction
How can fetal problems be diagnosed?
Measurement of uterine size
ultrasound scan
Causes of growth restriction?
Chromosomal anomaly (T21)
Viral infection (Rubella, CMV)
Severe Placental insufficiency
OR normal small baby (look at the parents)
Whats the difference between symmetrical/asymmetrical fetal growth restriction.
Measurement of head and abdomen. Symmetrical - both affected. Asymmetrical - abdomen only affected.
In fetal growth restriction, what does the size of the abdomen indicate?
size of the liver
If the circumference of the fetal abdomen is small what might this indicate?
Small liver resulting from a placental insufficiency and lack of glycogen
What are the consequences of hypoxia in the fetus?
Bloodflow redirected to the brain and away from gut, kidneys, lungs
Ultrasound findings in IUGR? 4 points
Small AC ( small liver) Decreased amniotic fluid ( this is produced by the kidneys) Increased blood flow to the brain (look at Middle Cerebral arteries in the brain – using the doppler effect scan
4 clinical features of IUGR
SFH smaller than expected
Baby’s movements lessen to conserve energy
Fetal heart rate changes as hypoxia develops (as seen on CTG)
Fetal death
what is Betamethasone/dexamethasone used for?
When given to the mother will cross the placenta and stimulate the aveoli cells to produce surfactant gene
Surfactant stops the collapse of the aveoli cells by coating the cells and reducing the surface tension
Helps prevent Respiratory Distress Syndrome which leads to neonatal death in premature babies
During pregnancy, by what mechanism is plasma volume increased? 5 points
Decreased thirst threshold
resetting of osmostat
Progesterone increases aldosterone release
oestrogen acts upon RAS
By how much does RBC mass increase by during pregnancy?
25%
What happens to white blood cells during pregnancy? 3 points
concentration remains the same
increase in neutrophils
Increase at delivery
What changes can occur to the heart during pregnancy? 3 points
Increase in size by up to 12%
May shift up in chest cavity
systolic murmurs are common
What happens to peripheral resistance during pregnancy?
Decreases by around 35%
What does the reduction in peripheral resistance not result in a drop in blood pressure during pregnancy?
Compensated for by an increase in cardiac output so blood pressure remains about the same.
What 2 changes occur to the respiratory system during pregnancy?
Increase in tidal flow
Increase in alveolar ventilation
What changes occur to the renal system during pregnancy and what stays the same?
Increase plasma flow and filtration rate.
Kidneys increase in size
Tubular reabsorption capacity remains the same so glucosuria is common
2 Common gastrointestinal changes in pregnancy?
Constipation
Reflux
What changes occur to glucose metabolism during pregnancy?
First Trimester - Insulin sensitivity
Second trimester - insulin resistance becausecortisol, progesterone, HPL, & oestrogen are all insulin antagonists
What protein hormones are released by the placenta?
hCG (human chorionic gonadotrophin)
hPL (human placental lactogen)
hPG (human placental gonadotrophin
CRH (corticotropin releasing hormone)
What steroid hormones are released by the placenta?
Progesterone
Oestrogen (oestriol)
What is HCG and what does it do? 3 points
Human chorionic gonadotrophin
Maintains corpus luteum secretion of progesterone & oestrogen
Decreases as the placental production of progesterone increases
What is hPL and what does it do? 4 points
Human Placental lactogen
Alters maternal carbohydrate and lipid metabolism to provide for foetal requirements
Mobilizing maternal free fatty acids
Inhibits maternal peripheral uptake of glucose
Increases insulin release from pancreas
Aim is a steady state of glucose for the fetus
What is hPG and what does it do? 3 points
Placental Growth Hormone secreted by the placenta responsible for regulating fetal growth
Induces maternal insulin resistance
What 4 functions does oestrogen serve during pregnancy?
Growth of the uterus, cervical changes
Development of ductal system of breasts
Stimulation of prolactin synthesis
Stimulation of corticol binding globulin (CBG), sex hormone binding globulin (SHBG), thyroxin binding globulin (TBG)
What is gestational diabetes?
Any abnormal glucose tolerance test after the first trimester
What problems is hyperglycemia associated with in the first trimester of pregnancy.? Give 3 examples
Fetal malformation Hydrocephaly Meningomyelocoele Central Cyanosis in Congenital Heart disease Single Ventricle &Sacral Dysgenesis Renal Agenesis
5 risk factors for maternal hyperglycaemia
Previous Gestational Diabetes Obesity Polycystic ovarian syndrome Family history of type 2 diabetes High risk racial group
3rd trimester problems caused by hyperglycaemia? 3 points
macrosomia
Pre-eclapsia
Fetal or Neonatal death
Management of hypergycaemina during pregnancy? 5 points
Folic acid 5mg in 1st Trimester
- Aspirin 75 - 150 mg/day from 12/40
- if less than 16/40
- Attendance at multidisciplinary one stop clinic
- Tight glucose control throughout pregnancy
- Fetal Ultrasound monitoring in last trimester
- Maternal monitoring of Fetal movements
What hormones are responsible for axillary and pubic hair?
adrenal androgens
Chronological order of pubertal development for boys and girls.
Growth spurt Breast development Pubic hair Axillary hair Menarche
Testicular volume Penile length Pubic hair Growth spurt Axillary / Facial hair Deep voice
What is Central or True precocious puberty dependent upon and how is it treated?
Gonadotrophin
LHRH analogue
What are the 3 concerns surrounding precocious puberty?
Possible underlying sinister cause
-Boys – upto 80%
Emotional & pyscho-social upheaval at an inappropriately young age
Early cessation of growth leading to decreased final adult height
In fetal development what two structures bind to from the kidney and ureter?
Mesonephric blastema and ureteric bud
If the mesonephric blastema and ureteric bud dont bind properly what can this result in?
Bifid ureter
Is a unilateral absent kidney usually a problem, what can this be associated with?
No.
Mayer-Rokitansky syndrome:
Abnormalities of the vagina (agenesis), uterus, fallopian tubes
Why are UTIs more of a cause for concern in infants?
Vesicoureteral reflux (VUR) most likely surgical cause rather than just infection.
What is VUR?
Vesicouretal reflux. Developmental abnormality in how the ureter enters the bladder means that there isnt enough of the ureter available to be squeezed shut each time the bladder empties and no urine in refluxed back up the ureter causing infection.
Complication of VUR?
If left untreated the infection can cause nephropathy.
What is PUV and what are the 2 complications associated with it?
Posterior uretheral valves.
Found in boys
Back pressure when trying to urinate can lead to damage if ureters and kidneys.
What is Hypospadias?
Malformation means that the meatus is not at the tip of the penis.
3 points to diagnose active labour
Painful regular contractions
Cervical effacement
Dilatation of the cervix of 4cms or more.
How is the progress of delivery measured?
Descent of the head in relation to ischial spines
What is the 2nd stage of labour
Full cervical dilation to delivery
Name the two fontanelles important in delivery
bregma (anterior)
posterior
Smallest and most common delivery angle of fetal skull
Suboccipitobregmatic
What is the 3rd stage of labour and how is this managed?
Delivery of placenta
.Active management (CCT)
Oxytocin i.m.
Physiological: Mother naturally expels the placenta and membranes with contractions
3 types of fetal monitoring during labour
Intermittent auscultation by Pinard or Sonicaid
CTG (cardiotocograph)
FBS
definition of congenital abnormality
Congenital anomaly: abnormality of structure, function or disorder of metabolism that is present at birth and results in a physical or mental disability
Most common and severe congenital anomalies? 3 points
heart defects, neural tube defects and Down syndrome
Most common causes of congenital defects? 4 points
Idiopathic 50%
Genetic
Infections
Teta
What are the 4 classifications of congenital structural abnormalities ?
Malformation: flawed development of a structure or organ (eg. transposition of the great arteries)
Disruption: alteration of an already formed organ (vascular event eg bowel atresia)
Deformation: alteration in structure caused by extrinsic pressures (mechanical eg talipes due to reduced liquor)
Dysplasia: abnormal organisation of cells
or tissues
