11 Flashcards
Describe follicular phase of menstrual cycle.
- Hypothalamus releases GnRH.
- Stimulates anterior pituitary to produce LH and FSH.
There are primordial follicles in ovaries. Each month, only some mature into primary follicles and only 1 will ovulate and produce an egg.
- So, in the beginning of menstrual cycle, GnRH is increased.
- This causes a small increase, then steady decrease of FSH.
- It causes a steady level of LH.
- FSH stimulates maturation of primary follicles, so some primary follicles will mature into secondary follicles.
- While these follicles are maturing, they produce oestrogen.
- In the first 10 days of the cycle, oestrogen has a negative feedback effect on the pituitary gland, inhibiting LH.
- So, at low concentrations, oestrogen inhibits LH.
- When oestrogen levels rise, FSH levels fall - this is why FSH falls when there is an increase in oestrogen from the follicles.
- After 10 days, oestrogen levels continue to rise, it then switch to having a positive feedback effect.
- It now stimulates the production of LH. Spike in LH concentration.
- This causes the ovulation of the most mature follicle in the ovary.
- Egg is released at day 14.
Describe luteal phase of menstrual cycle.
- After ovulation, LH levels drop.
- After the follicle ovulates, the follicle will turn into a corpus luteum.
The corpus luteum secretes:
- Oestrogen
- Inhibin
- Progesterone
- At 21 days, progesterone levels are increasing along with inhibin (Inhibin has a negative feedback mechanism and inhibits secretion of FSH because we do not need anymore follicles to mature yet).
- Progesterone inhibits the release of GnRH.
- In the luteal phase, progesterone levels increase slowly and oestrogen levels decrease, which suppresses GnRH release.
- Progesterone stimulates endometrial growth.
- As corpus luteum degenerates, all of the hormones it was secreting also reduce.
- Because oestrogen and progesterone are low, they cannot maintain the endometrial lining, therefore it sheds.
Where are FSH and LH from?
Anterior pituitary gland
What is the main hormone in the follicular phase?
Oestrogen
What is the main hormone in the luteal phase?
Progesterone
What is the name of a fertilised egg?
Zygote
What is the first epithelium?
Ectoderm
What is the site of fertilisation?
Ampullary-Isthmic junction of the oviduct
Can fresh sperm fertilise an egg?
No
What happens in capacitation?
- Hyperactivation (whip like action of flagella)
- Removal of acrosome
What is capacitation driven by?
Calcium
What 2 enzymes does the acrosome contain?
- Hyalruonidase (digests through cumalus)
- Acrosin (digests through zona pellucida)
How does the sperm penetrate the corona radiata?
By releasing hyaluronidase as the acrosome perforates, it enables sperm to push through granulosa cells.
How does the sperm penetrate the zona pellucida?
- Receptors on acrosome bind to ZP3 molecules which causes the release of acrosin
- Acrosin digests the zona pellucida
Describe sperm oocyte binding
- Membrane of oocyte and sperm fuse via integrin receptors.
- Sperm nucleus enters oocyte cytoplasm.
What does the trophoblast form?
The placenta
What does the inner cell mass form?
The embryo
What is fast block?
Prevents polyspermy when the membrane fusion causes the oocyte to depolarises
What is slow block?
Ca2+ enters the oocyte which causes the release of cortical granules containing hydrolytic enzymes which degrade the zona pellucida.
How does the 2nd meiotic division occur?
Calcium influx causes the oocyte to complete meiosis producing 2 haploid cells:
- Female pronucleus - majority of cytoplasm
- Second polar body - almost no cytoplasm
How do the pronuclei form?
- Nucleus of sperm enlarges to form pronuclei
- DNA within each pronucleus is replicated
Which stage of meiosis is the egg arrested in?
Metaphase
What is the best indicator of fertilisation?
Presence of second polar body
Give examples of types of abnormal fertilsation.
Parthenogenetic - egg activated without sperm - 1 pronucleus
Polyspermic - 3pn (2 male pronuclei and 1 female) - won’t develop
Meiotic error - DIGYNIC - 3pn (2 female pronuclei and 1 male) - may cleave but won’t get to blastocyst stage
What does the blastocyst signal to the corpus luteum?
To maintain progesterone levels
Describe hCG levels up to the first trimester?
Levels high initially to support and maintain progesterone production but then decreases after 12 weeks
List maternal cardiovascular changes in pregnancy?
- Increase in HR
- Increase in blood volume
- BP remains unchanged (more likely to be hypotensive)
- Haematocrit falls
What are the foetal changes to HR in pregnancy?
- HR rises to about 180bpm in T1
- Weight increases steadily
What are the 2 differentiated layers of the trophoblast?
Syncytiotrophoblast - multicellular located nearest to endometrium
Cytotrophoblast - unicellular (original trophoblast) located nearest to inner cell mass
How does the syncytiotrophoblast invade the endometrium?
By extending vili (projections )
It releases enzymes to break down the glycogen rich endometrial stroma
What are lacunae formed from?
Vacuoles in syncytium
What do maternal capillaries expand to form?
Sinusoids
Which then anastomose with lacunae
What is hCG produced by?
Syncytiotrophoblast
What are the physical effects on the mother in early pregnancy?
- Menses suppression
- Fatigue
- Enlarged breasts
- Nausea/vomiting
- Urinary frequency
- Constipation
What is the name of the part of the decidua which covers the foetus?
Decidua capularis
Which of the three regions of the decidua are considered to constitute the maternal portion of the placenta?
Decidua basalis
Which arteries supply the maternal blood to the placenta?
Endometrial arteries
What is the pO2 of maternal placental blood?
50mmHg
What is the pO2 of foetal blood?
30mmHg
How does the placenta function as a transporting organ?
- Allows exchange of respiratory gases
- Lipoprotein lipase allows foetus to take up fats
- Allows glucose to get into foetus
How does the placenta function as an endocrine organ?
hCG maintains CL (corpus luteum which releases P4) and stimulates thyroid
Progesterone - causes decidualisation, increases oviductal/uterine secretions and reduces uterine contractions
Oestrogens - androgens transported to placenta and converted to oestrogen which then can relax pelvic ligaments and pubic symphysis
What occurs in T2?
- Increased growth - triple in size and weight increases 30x
- Hypervolemia
- hCG falls and CL regresses
How is cholesterol converted to progesterone?
Cholesterol (from mother) –> pregenolone –> progesterone
What is Chadwick’s sign?
Blue-ish hue to vagina and labia at around 6 weeks
What happens to stroke volume in pregnancy?
Increases by 20%
What happens to the diaphragm in pregnancy?
Diaphragm is elevated by 4cm
What happens to tidal volume in pregnancy?
Increases
What happens to breathing in pregnancy?
Becomes thoracic
What happens to PCO2 responsiveness in pregnancy?
Increases
What happens to the kidneys in pregnancy?
- Enlarge
- Increased reabsorption of Na+
- Increased excretion of waste
What happens to ureters in pregnancy?
- Enlarge
- Displaced
What happens to bladder in pregnancy?
- Decreased bladder tone
- Urinary reflux from bladder to ureters
- Increased risk of UTIs
What happens to the breast in pregnancy?
- Stroma bulk increases
- Lobules increase
- Areola darken
- Nipples darken and become more pronounced
- Lactiferous ducts explained and branch for milk delivery
How does progesterone affect fluids?
Increases vasodilation and therefore less peripheral resistance and increased blood volume
What effect does oestrogen have on fluids?
Increased oestrogen causes:
- Increased AngII
- Increased renal Na+ reabsorption
- Increased aldosterone
What effect does oestrogen have on the breast?
Stimulates growth and development of milk duct
What effect does progesterone have on the breast?
Causes growth of alveoli and lobules
What effects does hPL have on the breast?
Mimics prolactin and GH
Which causes growth of the breast, nipple + areola
List T3 foetal changes.
- Fat deposition
- Double in weight
- Lung development
- Head towards pelvic brim - engagement
List T3 maternal changes.
- Relaxin produced - pelvic ligaments loosened
- Back pain
- Braxton-Hicks
- Colostrum
What is the required extra kilo calories for mothers?
200-300 kilo calories
What is spina bifida caused by?
Folate deficiency
What are genetic aetiologies of birth defects?
Consanguinity - small genetic pool resulting in recessive genes being more likely to be passed on
Which common infections can cause birth defects (congenital anomalies)?
TORCH
- Toxoplasmosis
- Other (Syphilis, Varicella-Zoster)
- Rubella
- Cytomegalovirus (CMV)
- Herpes
What can low maternal iodine cause?
Hypothyroidism and developmental delay
What can low maternal folate cause?
Spina bifida and neural tube defects
Which disease can cause sacral agenesis and what is it?
- Diabetes mellitus
- Sacrum doesn’t form properly
Which vitamin in excess can harm unborn baby?
A
What are the most common single primary defects?
- Developmental dysplasia of the hip
- Talipes
- Cleft lip/ palate
- Cardiac septal defects
- Neural tube defects
What happens in a malformation during development?
- Arise during the initial formation
- Result of genetic and/ or environmental factors
- Organogenesis e.g. cleft palate and cardiac septal defect
What happens if there is disruption during development?
Alters normal structures after their formation
2 basic mechanisms:
Amniotic band - fibrous band develops in utero causing a lack of blood supply to the limb - baby born with missing limb
Cardiovascular accident - e.g. Poland anomaly where there is an interruption of the subclavian artery supply which prevents blood supply to pectoral muscle.
What is a sequence malformation and an example?
When there is one single defect which then causes a sequence of events to occur
- Pierre Robin sequence - small jaw, tongue which falls back, cleft palate
What is Holt-Oram syndrome?
Characterised by skeletal abnormalities of the hands and arms (upper limbs) and 75% chance of heart problems.
At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals.
~75% of individuals with Holt-Oram syndrome have heart problems:
- Septal defects (atrial or ventricular)
- Cardiac conduction disease –> bradycardia or fibrillation
What is multiple malformation syndrome?
One or more developmental anomalies of 2 or more systems - common aetiology
What is Rubenstein-Taybi syndrome?
- Autosomal dominant
- CREBBP gene mutation
- Short stature
- Broad thumbs and first toesp
When is the newborn screening examination?
First 3 days of life
What does the newborn screening examination examine?
- Measures head
- Check hips
- Check eyes
- Listen to heart
- Check for absent red reflex - congenital cataracts
What are the reasons for antenatal care?
- Monitor progress of pregnancy
- Develop partnership between woman and professional
- Promote choice
- Recognise deviations from the norm
- Increase understanding of public health issues
- Provide opportunities to prepare for birth and parenthood
How many visits for parous women?
7
How many visits for nulliparous women?
10
When is it recommended the booking visit is done by?
10 weeks
Why are pregnant women more at risk of varicosities?
- Relaxed blood vessels
- Increased blood volume
What could proteinuria in pregnancy indicate?
Hypertension
If the foetus is measured at the umbilicus how many weeks are you?
24
Where is the foramen ovale?
Between right and left atria
Where is the ductus arteriosis?
From pulmonary artery to aorta
What are the 5 stages of lung development?
- Embryonic stage - 3-5wks
- Pseudoglandular stage - 6-16wks
- Canalicular stage - 17-24wks
- Saccular stage - 25wks-birth
- Alveolar stage - 36wks to childhood
What happens if a baby is born before surfactant production?
Respiratory distress syndrome - lung collapse
What is the effect of metabolic acidosis on surfactant production?
Reduces amount of surfactant produced
What can reduce surfactant production?
- Meconium aspiration
- Hypothermia
- Infection
- Prematurity
What is Potters syndrome?
In Potters syndrome you have no kidneys, so produce no urine to take up for the lungs to develop
What supplies oxygenated blood to foetus?
Umbilical vein passes through IVC to heart
What adaptation of the foetus allows the liver to be bypassed?
Ductus venosus - umbilical vein to IVC
What other adaptations of the foetal circulation are there?
- Foramen ovale - between RA and LA
- Ductus arteriosus - between pulmonary artery and aorta
What is the role of the umbilical arteries?
- 2 of them
- Carry deoxygenated blood from foetus to placenta
What is the fate of the ductus venosus?
Becomes ligamentum venosus
What happens in transposition of great arteries?
- RV gives rise to aorta
- LV gives rise to pulmonary artery
What happens in persistent pulmonary hypertension of the newborn?
- Stiff lungs so pulmonary arterioles stay constricted
- Pulmonary pressure high
- Blood difficult to pump through lungs
- Easier to go through ductus arteriosus
Name sites of red blood cell production from foetus to birth.
Yolk sac –> liver –> spleen –> bone marrow
If a mother is taking beta blockers, what effect can this have on the child?
Can stop babies response to hypoglycaemia
If a mother has polycythaemia, what effect can this have on the child?
Can cause the child to be hypoglycaemic as the RBC require a lot of glucose
When is the first stage of labour?
lao Onset of regular contractions
o Dilation of the cervix to from 3-4cm to 10cm (full dilation)
o Sometimes Braxton Hicks can be felt for up to a week before labour
What is the latent phase of labour?
o Onset of contractions to regular contractions
o 3-4cm dilatation, cervix fully effaced (softened + thinned down)
o Uterine muscle tone is increasing
o Cervix changes from tubular structure to a thin membrane in response to head pushing against cervix –> prostaglandin releases –> cervix softs and thins
How long usually is the first stage of labour for the first baby?
8-10 hrs
How long is the first stage of labour for the 2nd onwards baby?
2-6 hrs
When is the 2nd stage of labour?
Time from full dilation to delivery of the baby
When is the 3rd stage of labour?
From the delivery of the baby to the delivery of the placenta + its membranes
What drugs are used in the 3rd stage of labour?
- Ergometrine
- Oxytocin
- To cause to uterine to contract so the placenta can be delivered
At how many weeks would you find 2 milk lines from axilla to groin?
4 weeks
At how many weeks would you find milk hills?
7-8 weeks
When are the primary milk ducts formed?
32 weeks
What is the role of oestrogen in the breast?
- Stimulates ductal system proliferation and differentiation
- Causes ducts to lengthen and branch out = bigger breasts
What is the role of progesterone in the breast?
- Duct enlargement and widening
- Causes lobes, lobules and alveoli to grow
What is the influence of prolactin in the breast?
- Causes the nipple to grow
- Essential for alveolar-lobular development
What is the role of serum placental lactogen in the breast?
Areola growth
How many sebaceous glands does the areola contain?
Around 20
What connects to alveoli via ducts?
Nipple
What are the tubercles of montgomery?
Alveolar gland and sebaceous gland
What is the name of the secretory units and where are they located?
- Alveoli
- At terminal ductules
What surrounds the alveoli?
Myoepithelial cells
Which hormone do myoepithelial cells respond to
Oxytocin
Where would you find lactocytes?
Lining the alveoli
Which nerve innervates the areola and nipple?
Intercostal nerve
What is the arterial supply of the mammary gland?
60% from internal mammary artery
30% from lateral thoracic artery
What is the innervation of the mammary gland?
2nd -6th intercostal nerve
What is the milk secreting unit of the breast?
The mammary gland
What are the breast changes in pregnant women?
- Nodular to touch
- Tingling
- Tenderness
- More prominent veins
- Increased pigmentation in nipple
- Bigger areolas
- Colostrum comes out at 12-16wks
What are the stages of lactation?
- Mammogenesis
- Lactogenesis 1
- Lactogenesis 2
- Lactogenesis 3
- Involution
What is the prolactin receptor theory?
Prolactin receptors in wall of alveoli distort shape when breasts are full of milk so prolactin detaches from the receptors causing decreased milk production therefore frequent suckling increases prolactin receptors and milk production.
Describe the let down reflex (milk ejection).
Oxytocin from hypothalamus to posterior pituitary which then goes to the myoepithelial cells causing the milk to be squeezed out of the mammary glands into the milk ducts.
What are inhibitors of milk production?
- Placenta fragments
- Interruption of milk removal
What are the inhibitors of milk ejection?
- Stress
- Pain
- (Limbic system)
When are prolactin levels highest?
At night
What effect does prolactin have on ovulation?
Suppresses it
What is involution?
When the mother begins to feed the baby solid foods at around 6 months, there is decreased suckling and decreased prolactin production.
What are the advantages of human milk?
- Immunity
- Perfect balance of hormones and micronutrients
- Balanced diet
What are the disadvantages of formula milk?
- Processed
- Expensive
- Unsterile
What is the main bacteria involved in infective mastitis?
Staphylococcus aureus
How would you treat infective mastitis?
Warm compress
Keep breastfeeding
What are the causes of non-infective mastitis?
- Back pressure which causes milk to leak via paracellular pathway
- Poor positing/latching etc.
What signs could indicate thromboembolism?
Unilateral calf pain
Redness/swelling
What signs could indicate infection after birth?
- Offensive smell lochia (vaginal discharge)
- Pain in breasts, abdomen + perineum
- May feel generally unwell
What is a red flag sign for pre-eclampsia?
- History of hypertension
- Visual disturbances
How long do babies survive on colostrum for?
3 days
When is CF and sickle cell disease tested for?
In the heel prick test
When is the acoustic hearing test carried out?
24-36hrs
What is the biggest cause of maternal death?
Suicide
What is plasma?
Blood with all the cells removed but with plasma proteins still in
What is serum?
Blood with all cells and coagulation proteins removed
What would an increased prothrombin time indicate?
Early indication of liver disease
What does Guthrie test test for?
PKU
What is PKU?
Dysfunction of phenylalanine hydroxylase enzyme which normally converts phenylalanine to tyrosine.
Accumulation of phenylalanine and no downstream products of tyrosine.
What does a high ALP suggest?
Activity is increased in liver due to synthesis by the bile canaliculi in response to cholestasis.
What is a key feature of chronic liver disease?
Hypoalbuminaemia
What is a teratogen?
Directly or indirectly causes structural or functional abnormalities in the foetus or child after birth if administered to pregnant woman
What effect can tobacco have on developing foetus?
Can cause placental abruption and premature birth
What is behavioural teratology?
Impaired behaviour due to physiological birth defect
What is the difference between mendelian inheritance and multifactorial?
Mendelian - everything independent therefore obstetric history does not impact
Multifactorial - combination of factors e.g. genetic and environmental
How can drugs be transferred across the placenta?
- Passive diffusion
- Facilitated diffusion
- Active transport
What is drug transfer across the placenta influenced by?
- Molecular weight
- Lipid solubility
- Ionisation
- Protein binding
- Chemical structure
What is passive diffusion across the placenta increased by?
- High lipid solubility
- Low protein binding
- High maternal level of drug
What could exposure to drug at 24 days cause?
Ancephaly
What could exposure to drug at 12-40 days cause?
Limb reduction
What could exposure to drug at 34 days cause?
Transposition of great vessels
What could exposure to drug at 36 days cause?
Cleft lip
What could exposure to drug at 42 days cause?
- Ventricular septal defect
- Syndactyly
What could exposure to drug at 84 days cause?
Hypospadias
What are the factors in calculating optimal weight of newborn?
- Altitude - Nepal have smaller babies due to low O2
- Maternal height
- Maternal weight - bigger mother = bigger baby
- Gestational age - late bookers may not have known they were pregnant
- Parity - first baby smallest
- Foetal gender - boys bigger
- Ethnic group - hispanic bigger babies
What is the definition of a small for gestational age baby?
Babies birthweight below 10th percentile for gestational age
What is the definition of intrauterine growth restricted baby?
Baby that has not reached growth potential because of environmental and genetic factors.
What are the phases of foetal growth?
0-14wks - cell hyperplasia
15-32wks - cell hyperplasia and hypertrophy
32wks+ - cell hypertrophy and fat deposition
What are the causes of symmetrical growth restriction?
- Chemical exposure
- Viral infection
- Chromosomal
What are the causes of asymmetrical growth restriction?
- Pre-eclampsia
- Placental insufficiency
Is a symmetrical growth restriction a result of an early or late insult?
Early
What is a symmetrical growth restriction?
Both small head and abdomen
Is an asymmetrical growth restriction a result of an early or late insult?
Late
What is an asymmetrical growth restriction?
Normal sized head and small abdomen.
Have reduced liver size and decreased fat deposition.
What are the maternal factors of growth restriction?
- Smoking
- Alcohol
- Anaemia
- Disease
What are the foetal factors of growth restriction?
Structural abnormalities e.g. bowel outside of body
TORCH
- Toxoplasmosis
- Other (Syphilis, Varicella-Zoster)
- Rubella
- Cytomegalovirus (CMV)
- Herpes
What are the placental factors of growth restriction?
Placenta praevia - placenta blocks neck of uterus so interferes with normal delivery
Abruptio placenta - premature separation of placenta from uterus
Thrombosis/infarction
Oedema/vasculitis
What are the uterine factors of growth restriction?
- Decreased uterine blood flow
- Pre-eclampsia
- Atherosclerosis of uterine spiral arteries
Which measurements should be made with ultrasound to detect small baby?
- Abdominal circumference
- Head circumference
- Femur length
- Liquor volume - amniotic fluid
What is the Barker hypothesis?
IUGR can increase risk of adult metabolic syndrome - hypertension, type II diabetes, stroke and IHD
Which drug use in pregnancy can cause floppy infant syndrome
Benzodiazepines
What can narcotic use in pregnancy cause?
Neonatal respiratory depression
What can warfarin use in pregnancy cause?
Foetal haemorrhage
What can ACE inhibitors in pregnancy cause?
- Oligohydraminous
- Growth retardation
- Hypocalvaria
- Neonatal convulsions
- Hypotension
- Anuria
What can anti epileptics in pregnancy cause?
- Possible mental retardation
- Autism