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
Why is it better to talk with children than talk to children?
Talking with encourages discussion and the child can take responsibility for their illness.
Talking to is quite formal, the child is left out and suggests you do not want to listen to the child.
What is meant by the stage of the child?
Stage is where child is at in developmental terms
At what age would you expect the child to be babbling?
3-6mnths
Which factors can affect communication with children?
- Hearing impairments
- Speech may be affected by things such as cleft palates
- Visual impairment
- Major life events
- If unwell may not want to talk
What are the 4 golden rules for questions when talking to children?
- Use open questions
- Only questions that are needed
- Don’t use why question
- Never ask questions to satisfy own curiosity
What is development?
Increase in complexity of organism due to maturation of nervous system
What are the areas of development?
- Gross motor - walking
- Fine motor
- Speech
- Hearing
- Vision
- Social
- Language
- Speech
What could a delay in speech be caused by?
- Cleft palate
- ASD
- Hearing loss
- Environmental deprivation
What are causes of developmental delay?
- Perinatal hypoxia
- Congenital infection
- Cerebral malformation
- Genetic syndromes - e.g. trisomy 21
What % of children by 1yrs old are walking?
50%
What are the 4 phases of growth?
- Foetal
- Infancy
- Pre-pubertal
- Puberty
What is the slowest phase of growth and which hormone is it controlled by?
- Pre-pubertal
- Growth hormone
At what age should you be able to draw a circle, square and triangle?
3, 4, 5
What is the pattern of weight loss/gain in the first 2 weeks of life?
Week 1 lose 10% of birthweight
Week 2 regain that loss
What is failure to thrive?
Suboptimal weight gain in infants and toddlers
Most lie below 2nd centile
What are complex causes of failure to thrive?
- Inadequate retention - allergies, GORD
- Inadequate intake - wrong milk, poor technique
- Malabsorption - CF, CMPI, necrotising enterocolitis
- Increased requirement - CF, thyrotoxicosis
How do you work out BMI?
Weight (kg) / Height (m^2)
What are the rankings of BMI?
< 18.5 - underweight
18.5-25 - normal
26-30 - overweight
>30 - obese
Height velocity during puberty?
9cm per year
Height velocity before puberty?
4.5cm per year
When is foetal growth at its greatest?
Between week 16 and 20 of gestation
Growth is characterised by an increase in what?
- Cell size
- Cell number
- Intracellular volume
What happens to each system in senescence?
Brain - decrease in memory + impairment in coordination
CVS - decreased blood flow and arteriosclerosis
Lungs - decreased elasticity and lung function
GI - decreased GI muscle tone and peristalsis
Pancreas - decreased hormone production and sensitivity
Genitals - menopause
Bone - decreased bone deposition + degenerative changes in joints
Skin - loss of elasticity
Muscle - decreases
Describe the areas of bone growth.
- Proliferation zone
- Chondroblasts quickly divide and push epiphysis away from diaphysis (this lengthens bone) - Hypertrophic zone
- Older chondrocytes enlarge and signal to surrounding matrix to calcify - Calcification zone
- Matrix bones calcified
- Chondrocytes die leaving behind trabculae-shaped calcified cartilage - Ossification zone
- Osteoclasts digest calcified cartilage
- Osteoblasts replace it with actual bone tissue in the shape of calcified cartilage
- Results in bone trabeculae
Where is growth hormone produced?
Anterior pituitary gland
What are the indirect actions of GH mediated by?
IGF
Which of the IGF’s rises in childhood to peak at puberty?
IGF-I
Which of the IGF’s plays a role in foetus before birth?
IGF-II
What can overexpression of IGF-II in foetuses cause?
Disproportionate growth of tongue, kidney, heart, liver and muscle
What other mediators are involved in growth?
Platelet-derived growth factor Fibroblast growth factor Nerve growth factor Thyroid hormones Prolactin Insulin Placental lactogen Vitamin D PTH Oestrogen and Testosterone
When does secretion of T3 and T4 occur?
15-20 weeks of gestation
Why are thyroid hormones essential for growth in the foetus?
Essential for protein synthesis in brain
Essential for normal differentiation and maturation of skeleton and nervous tissue
Inadequate levels of thyroid hormone can lead to cretinism
What does the absence of thyroid hormones in the foetus cause?
- Cretinism
- Decreased size and number of cerebral cortical neurons
- Reduction in degree of branching of dendrites and synapses
- Deficiencies in myelination of nerve fibres
- Reduced blood supply to brain
What is the effect of cortisol on growth?
Inhibitory
Which hormones interact to cause the pubertal growth spurt?
- GH
- Sex hormones
- IGF-I
What stimulates GH in girls?
Oestradiol-17B from ovaries
What stimulates GH in boys?
Testosterone from testicular leydig cells
What is GH structurally similar to?
Prolactin and human placental lactogen
What is the effect of stress and exercise on GH?
Increases it
How is GH secretion regulated?
Hypothalamus produces GHRH which causes GH release from the anterior pituitary
GH causes the production of IGF-I
IGF-I then directly inhibits GH by inhibiting somatotrophs (these release the GH)
IGF-I indirectly inhibits GH by inhibiting GHRH release from hypothalamus
IGF-I also indirectly inhibits GH by stimulating somatostatin (which is an inhibitor of GH)
Describe achondroplasia.
- Autosomal dominant
- Mutation in chromosome 6 on FGFR3 gene
Mutation results in:
- Decreased endochondral ossification
- Inhibited proliferation of chondrocytes
- Decreased cellular hypertrophy
Describe acromegaly.
(Giantism in adults)
Hypersecretion of GH.
Most often caused by adenoma of pituitary somatotroph cells.
Actions of GH and IGF-I affect all organs and soft tissue so you get enlarged hands, feet, tongue, lips, nose, jaw etc.
Impaired glucose tolerance.
What is giantism?
Hypersecretion of GH in children
What is the cause of pituitary dwarfism?
- GH deficiency in childhood
- Caused by pituitary or hypothalamic tumours, infections, pituitary infarction, vascular malformations and head trauma
- Treated with recombinant IGF-I
How might children with hypothyroidism present?
- Puffy face
- Dry brittle hair
- Low hair line
- Jaundice
- Choke frequently
- Have constipation
- Don’t cry much
- Sleep a lot
What is the biggest cause of growth failure worldwide?
Malnutrition
Where is milk stored prior to being expressed
In the alveoli of the lactiferous duct
How do oligosaccharides in breast milk work?
They are not present in infant milk and are not digested by the infant.
Instead they make up intestinal flora by acting as decoy receptors for pathogens.
What is the arterial supply to the breast?
Mammary branches of lateral thoracic artery.
Thoracoacromial branches.
Medial mammary branches of perforating arteries.
What does breast tissue sit on directly?
Pectoral fascia which overlies pectoralis major
Where is the retromammary space?
Potential space between pectoral fascia and breast
Where is the main lymphatic drainage of the breast to?
Axillary nodes
Define preterm.
Born alive before 37wks
Define term.
Born 39wks to 40wks and 6 days
Define post term.
Beyond 42wks
Define neonate.
Baby in first 4 weeks of life.
What can happen with the eyes of a premature baby?
Retinopathy of prematurity where there is bleeding in the eye as vessels have not formed properly.
What can happen with the hearing of a premature baby?
Ears not fully developed until 26wks
What can happen with the CNS of a premature baby?
Before 32wks susceptible to intraventricular haemorrhage
Hypoxic ischaemic encephalopathy - swelling and irritation to brain caused by lack of oxygen
What are the metabolic effects of a premature baby?
Hyperbilirubinaemia
Hypoglycaemia
What is surfactant produced by?
Type II pneumocytes
What is the role of surfactant in a baby?
- Prevent atelectasis
- Increase pulmonary compliance
At what age should a baby smile?
4-6wks
When should the baby talk in short sentences?
2yrs
What are some causes of deafness in children?
- Glue ear
- Auditory neuropathic spectrum disorder - where the sound is received normally by the cochlea but is distorted on way to brain
- Cholesteatoma - collection of skin in ear
- Congenital CMV - causes sensorineural deafness
- Meningitis
- Syndromes - Alport, Crouzon
- Microtia - underdevelopment of pinna
- Atresia - lack of ear canal
Which drugs can cause permanent deafness?
- Some aminoglycosides e.g. gentamicin
- Some chemotherapy drugs e.g. cisplatin and carboplatin
Which drugs can cause temporary deafness?
- Quinines
- Aspirin
- Loop diuretics
At what age may a child be shy with strangers?
5-10mths
At what age should a child roll over?
2-3mths
At what age should a child walk?
1yrs
At what age should a child sit?
6mths
How can Duchenne Muscular Dystrophy be diagnosed?
Serum enzymes, biopsy and EMG
Which serum enzymes may be elevated in DMD?
Creatine phosphate
What replaces muscle fibres in DMD?
Fat and connective tissue
What is the inheritance pattern of DMD?
X-linked recessive
Only affects boys, female carriers
What is the role of dystrophin?
Stabilises muscle cell during contraction
What happens if dystrophin is down regulated, as it is in DMD?
Poorly anchored fibres tear themselves apart and free calcium can then enter muscle cells causing cell death and fibre necrosis.
How is creatine phosphate produced?
When muscle is resting, it produces too much ATP for a resting muscle so:
Creatine + ATP –> Creatine phosphate + ADP
Then the phosphate can be utilised when the muscle starts to contract again
What is the inheritance pattern of sickle cell disease and how can it affect pregnancy?
Autosomal recessive.
Women with sickle cell disease more likely to have premature baby or LBW baby
What is the inheritance pattern of CF and how does it affect pregnancy?
Autosomal recessive.
Can be detected by amniocentesis or chorionic villi sampling.
What is the process of PCR?
- Denaturation
- Heated to 90 degrees to break DS DNA to SS DNA - Annealing
- Reaction temp lowered to 50-65 degrees to allow annealing of primers - Extension
- Temp increased to 72 degrees
- Nucleotides in solution are added to annealed primers by DNA polymerase
- Creates new strand of DNA complementary to each single strand template
How much do infants grow in 1st year?
25cm
Which cell does LH act on in males?
Leydig cells
What is the effect of LH on leydig cells?
Causes the production of testosterone in the seminiferous tubules
What is the effect of testosterone on LH and GnRH?
Suppresses it
What converts testosterone to dihydrotestosterone?
5-alpha reductase
What cell does FSH act on in males?
Sertoli cell
What is the effect of FSH on sertoli cell?
Causes the release of androgen-binding protein which then binds to testosterone to maintain high levels
Where is inhibin released from in males and what is its effect?
- Sertoli cells
- Inhibits FSH
What is the perineal body?
Where is it?
Fibromuscular mass between opening of vagina + rectum.
The midline of the perineum is linked to the pelvic floor.
Why is the perineal body important?
May rupture during vaginal delivery leading to prolapse of uterus, bladder, rectum because it’s linked to pelvic floor.
At what point in the course of the pudendal nerve would you administer a nerve block?
Near ischial spine where it courses around the sacrospinous ligament
What would be anaesthetised during a pudendal nerve blood?
The posterior perineum (anal triangle) but not anterior or lateral parts of vulva.
When would you consider anaesthetising pudendal nerve?
Provide analgesia for 2nd stage of labour
Repair of episiotomy or perineal laceration
Outlet instrumental delivery
Minor surgery to lower vagina + perineum
What structures can be damaged if the perineum tears?
Which structures must be avoided when carrying out an episiotomy?
Muscles of anal sphincter - 3rd degree tears.
Laceration of rectal lining - 4th degree tears
What is an episiotomy?
Surgical cut in the muscular area between vagina + anus made just before delivery to enlarge vaginal opening.
Describe the blood supply of the structures of the perineum.
Internal pudendal artery (+ branches) and vein (and tributaries)
What are tributaries?
A vein that empties into a larger vein
Describe the innervation of the structure of the perineum.
Pudendal nerve and its branches (dorsal nerve of penis/clitoris, perineal nerve, posterior scrotal/labial nerves)
What are the main ligaments of the uterus?
Uterine ligaments:
- Uteroscaral
- Transverse cervical (cardinal)
- Pubocervical
- Round
- Broad - function = support the cervix + uterus
Name the spaces in behind the uterus + why it’s important.
Pouch of Douglas - can act as collection/drainage point at bottom of peritoneal cavity
Recto-uterine pouch aka pouch of Douglas
Pouch of Douglas is at risk of chronic endometriosis
Implicated for pus, ascites, tumour spreading, abdominal abscess, peritonitis
Name the space in front of the uterus.
Vesico-uterine pouch
aka Dunns Pouch
Vesico - vesical (bladder)
Utero - uterine (uterus)
Risk of endometriosis
What is endometriosis?
When tissue that behaves like the liming of the womb (endometrium) is found in other parts of the body.
What is the normal position of the uterus?
Anteverted + anteflexed.
When bladder full, uterus is horizontal.
What are the common variants of the uterus position?
Can be retroverted, into Dunn’s pouch (posterior angulation of uterus + cervix relative to vagina)
Retroflexed (posterior angulation or uterine corpus w/ respect to cervix
What does anteflexed mean?
Anterior angulation of uterus with respect to cervix
What are the histological features of ther uterus in the proliferative phase of the menstrual cycle?
Endometrium thickens
Endometrial stroma thickens + vascularised
Connective tissue renewed
What are the histological features of the uterus in the secretory phase of the menstrual cycle?
Spiral arterioles in stratum functionalis contract
Endometrium degenerates
Local ischaemia + loss of function
During the proliferative phase of the menstrual cycle, which layer of the uterus undergoes hypertrophy?
Endometrium
What is an ectopic pregnancy?
Implantation of blastocyst outside uterus - usually in oviduct.
Why is an ectopic pregnancy so dangerous?
Risk of ruptured oviduct, leading to internal bleeding, infection and shock.
Untreated ectopic pregnancy is a leading cause of 1st trimester maternal death.
What anatomical features of the oviducts and the peritoneum enable abdominal ectopic implantation?
Tubes open into peritoneal cavity at ostium hence there is a direct communication with the peritoneal cavity
What are the changes in the microanatomy of the ovary through the menstrual cycle and in pregnancy?
Follicular growth from pre-antral to antral with presence of cavity which then ruptures (ovulation).
Acquisition of LH receptors on Granulosa AND Thecal cells.
Formation of corpus luteum; the structure which produces progesterone and is maintained until menses (loss of luteal hormonal support) or prolonged in pregnancy.
What is the function of the corpus luteum?
Produces progesterone
Describe the arterial supply to the uterus and ovaries
Uterine artery (internal iliac), ovarian artery (aortic) and their anastomosis
What structures are closely related to the uterine arteries?
Distal parts of the ureters.
Describe the lymphatic drainage of the uterus and ovary.
Cervix - to external and internal iliac nodes and sacral nodes via uterosacral ligament;
Lower uterine body - to external iliac nodes;
Upper uterine body, fundus, uterine tubes and ovaries along ovarian arteries - to para-aortic nodes
Where does the lymphatics from the fundus drain into?
Para-aortic nodes
Where does the lymphatics from the lower uterine body drain into?
External iliac nodes;
Where does the lymphatics from the cervix drain into?
External + internal iliac nodes
Sacral nodes
- via uterosacral ligament;
Where does the lymphatics from the uterine tubes, ovaries and upper uterine body drain into?
Para-aortic nodes
During delivery, how does the fetus normally rotate/move to through the bony pelvis?
Flexion - places foetal head in optimal and smallest diameter, before internal rotation, where the fetal head rotates from occiput transverse to occiput anterior or posterior (occurs passively due to maternal pelvic shape.
Next, extension as face, head and chin are born.
Next, external rotation/restitution where baby rotates from face down to face inner thigh - time to identify shoulder dystocia.
Finally expulsion; anterior shoulder passes out, perineum distended by posterior shoulder and then an upward motion for delivery of rest of baby.
What S+S might cause a women to suspect she is pregnant?
Tender, swollen breasts
Nausea (+/- vomiting)
Polyuria
Fatigue
Food aversions/cravings
Cramping
Mood swings
Dizziness
Constipation
Darkening areola
Missed period
What is the name and function of the substance detected by a pregnancy test?
hCG - human chorionic gonadotrophin which signals and maintains the corpus luteum
Which cells secrete hCG ?
Secreted from syncytiotrophoblast cells.
What is the temporal pattern of hCG secretion?
Rises steadily from implantation until 8 weeks and then drops as placental production of progestogens takes over
Give two reasons why a positive result does not guarantee a full term pregnancy?
Detects hCG which may be produced by an ectopic/molar pregnancy
Indicates a “biochemical pregnancy’ but embryo/feotus may miscarry.
Which foetal membrane forms the foetal portion of the placenta?
The allantois forms from the yolk sac
The chorion forms from the trophoblast
The chorionic mesoderm and the amnion forms from the amniotic ectoderm and extraembryonic mesoderm
From what tissue does the maternal portion of the placenta form?
The placenta is embryonic-derived and is the junction between the embryonic component and the endometrium
The term decidua refers to the functional layer if the endometrium that is shed after birth.
It may be divided into three regions.
What is the name given to the region that covers the foetus?
Decidua capsularis
What is the name given to the remaining parts of the decidua, covering the remainder of the uterus?
Decidua parietalis
Which of the three regions of the decidua are considered to constitute the maternal portion of the placenta?
Decidua basalis
The foetal portion of the placenta forms part of the chorion. This part of the chorion is highly branched and has a very convoluted surface. What is this known as?
The villous chorion
Where is the smooth chorion located?
In contact with the decidua capsularis, eventually contacting the decidua parietalis
In the region of the placenta proper, lacunae form between the villous chorion and the decidua basalis, creating the intervillous space.
What is the origin of the blood within the intervillous space?
Maternal
The placental membrane (once known as the placental barrier) refers to the layers of tissue that separate the foetal vessels in the villi from the maternal blood in the intervillous space.
Which 3 structures make up the placental membrane?
Decidua capsularis
Decidua parietalis
Decidua basalis
What does the decidua capsularis merge with obliterating the uterine cavity?
Decidua parietalis
What region of decidua is the endomertrium that covers the implanted blastocyst?
Decidua capsularis
What is the decidua region between the blastocyte + myometrium?
Decidua basalis
What is oligohydramnios?
Deficiency of amniotic fluid (less than 400ml in later pregnancy)
What can oligohydramnios result from?
Renal agenesis - because the fetus is unable to contribute urine to the amniotic fluid volume
What is placenta previa?
The fetus implants in such a way that the placenta or fetal blood vessels grow to block the internal os of the uterus.
What are dizygotic twins?
Twins derived from 2 zygotes that were fertilised independently.
What are the chances that the 2 placentas associated with dizygotic twins are fused?
65% fused
35% not fused
How many amnions, chorions and placentas do monozygotic twins have?
2 amnions
1 chorion
1 placenta
How many amnions, chorions and placentas do dizygotic twins have?
2 amnions
2 chorion
2 placenta
What would cause monozygotic twins to have 1 amnion?
If embryo splits early in the second week after amniotic cavity has formed
What are the 3 circulatory shnts in foetal circulation known as?
Ductus venosus
Ductus arteriosus
Foramen ovale
What is the function of the ductus venosus?
Allows blood from placenta to bypass the liver
What do the ductus arteriosus + foramen ovale allow?
Blood to bypass the developing longs in foetus
What is the umbilical cord formed by?
Foetal connecting (body) stalk
Yolk sac
Amnion
What arteries + veins does the umbilical cord constrain?
R + L umbilical arteries
L umbilical vein
What can the presence of only one umbilical artery suggest?
Presence of cardiovascular anomalies.
What are the 3 functions of amniotic fluid?
Protects the foetus physically
Provides room for foetal movements
Helps regulate foetal body temperature
How is amniotic fluid produced?
By dialysis of maternal + foetal blood through blood vessels in the placenta.
Later production of foetal urine contributes to the volume of amniotic fluid
Foetal swallowing reduces it
What is the water content turn over of the amniotic fluid?
Every 3 hours
Name 3 groups of harmful substances that cross the placental membrane.
Give examples of each
Drugs:
- cocaine, alcohol, nicotine, warfarin, trimethadione, phenytoin, tetracycline, sedatives, analgesics, chemotherapeutic agents, caffeine
Infectious agents:
- Viruses (HIV, cytomegalovirus, rubella, coxsackie, variola, varicella, measles, poliomyelitis)
- Bacteria (tuberculosis, treponema)
- Protozoa (toxoplasma)
Poisonous gases
- Carbon monoxide
Name electrolytes that cross the placental membrane
Na+, K+, Cl-, Ca2+, PO42-
Name metabolites that cross the placental membrane
Carbon dioxide, urea, uric acid, bilirubin, creatine, creatinine
Name steroid hormones that cross the placental membrane.
Cortisol, oestrogen (unconjugated only)
Does serum albumin and some protein hormones (thyroxin, insulin) cross the placental membrane?
Yes
What is the foetal portion of the placenta known as?
Villous chorion
Which arteries supply the maternal blood to the placenta?
Endometrial arteries
In some instances the placenta forms completely or partially over the cervix, termed placenta praevia.
What complications do you think this could cause?
Bleeding during labour.
Placental abruption
Pre-term delivery
Pre-term premature rupture of membranes (PPROC)
Placental accreta (occurs in 5-10% of previa)
On which deep tissue does the breast lie on?
Deep pectoral fascia + the fascia of the serratus anterior
How much breast milk do women produce?
750 mL per day
What types of glands are located on the areola?
Montgomerey’s glands, provide lubricant during feeding. They are a type of sebaceous gland.
Also accessory mammary glands + sudoriferous glands
In which structure is milk stored prior to being expressed?
Within the alveoli of the Laciferous ducts
Hypertrophy of which tissue/structure gives rise to the increase in breast size associated with pregnancy?
The Laciferous Ducts - the duct/tubule/alveolar structure
Apart from the lateral thoracic and branches of the internal thoracic, which other smaller artery supplies the breast?
Pectoral branch of thoracoacromial artery
How do breast cancers can spread from one side to the other?
Through highly structured lymphatic system which has connections to the contralateral breast by passing across median plane.
Where does the breast lymph from these different groups of lymph nodes ultimately drain to?
Axillary lymph nodes (75%) or Phrenic nodes,
- Ultimately to the apical or inferior deep cervical (supraclavicular) nodes.
Following the blood from the placenta in the umbilical vein, how does this blood pass to the inferior vena cava (IVC)?
There is a shunt through the ductus venosus.
Most oxygenated blood from the IVC enters into the right atrium and flows through into the left atrium. Which feature of the foetal heart allows this to occur?
Foramen ovale
Where does most of the blood from the pulmonary trunk pass to, and what feature of the foetal circulatory system allows this to occur?
Passes through ductus arteriosis to caudal aorta
The richly oxygenated blood from the left atrium passes to the left ventricle and exits the heart via the aorta.
Which structures are supplied with this oxygen rich blood before it mixes with the lower oxygen content blood from the pulmonary trunk?
Heart + brain
Where does the blood in the descending aorta pass to?
Trunk + lower limbs
How does blood return to placenta?
Bilaterally via internal iliac + umbilical arteries
What happens to the. foramen ovale at birth + what remnants may be found in the adult?
Closes becomes the fossa ovalis.
Closure occurs due to drop in right arterial pressure
What happens to the ductus arteriosus at birth and what remnants may be found in the adult?
Contraction of this muscular artery occurs immediately after birth; anatomical closure occurs at 2-3 months after birth.
Forms Ligamentum Arteriosum.
What happens to the ductus venosus at birth and what remnants may be found in the adult?
Closes when PGE2 and PGI2 levels decline at birth, directing blood to liver. By 2-3 weeks closure is permanent, forming Ligamentum Venosum.
What happens to the umbilical vein at birth and what remnants may be found in the adult?
Closes within 1 week of birth, and replaced with Ligamentum Teres Hepatis
What happens to the umbilical arteries at birth + what remnants may be found in the adult?
Remain in adult;
Branch of anterior division of internal iliac artery.
Non patent part forms medial umbilical ligament.
Name the process by which spermatozoa and oocytes fuse.
Fertilisation
What is the oviduct also known as?
Fallopian tube
Which structure has the following function
Picks up the oocyte from ovary at ovulation using processes called fimbriae + transports oocyte to the ampullary-isthmus junction?
Oviduct
What does high P4 levels do?
Makes it so that the cervical mucus prevents sperm entering uterus
Which structure remains after ovulation and produces progesterone?
Corpus letuem
Oestrogen (OE2) and progesterone (P4) suppresses the production of. which hormones?
Gonadotropins (FSH and LH)
As corpus luteum regresses, P4 levels drop. What happs to gonadotrophin levels?
Begins to rise
Where does FSH act?
Granulosa cells of growing follicles
Where are LH receptors expressed?
Thecal cells
What effect does LH binding to receptors on theca cells have?
Rise in androgens which get converted into oestrogen and inhibin by granulosa cells
What does rising levels of oestrogen and inhibin lead to?
LH maintenance
FSH inhibition
What are the consequences of Oestrogen rise?
Granulosa expresses LH receptors LH surge (leads to ovulation)
What does progesterone do to LH?
Inhibits it
Which hormones does the corpus luteum begin producing?
Progesterone and oestrogen
Average sperm survival in female reproductive tract?
5 Days
Majority of sperm is transported to site of fertilisation (ampullary-isthmic junction) how?
Majority of the transport is via muscular contractions of the uterus and oviduct
Once at the oviduct, the cilia lining fallopian tube beat sperm in right direction
What is capacitation?
Process whereby sperm is activated
Describe capacitation
Membrane changes (acrosomal reactions) and flagella starts moving once sperm is away from seminal plasma and epididymis fluid
These processes are both calcium dependent
What is the acrosome?
Head of the sperm
What does the acrosome contain?
Enzymes to digest (acrosin) through zona pellucida (thick membrane of egg)
An ovulated oocyte is at which stage of. meiosis?
Metaphase 2
A capacitated, activated sperm can digest its way through cumulus cells and binds to what?
Glycoproteins on the zona pellucida (ZP2/3)
Binding of sperm with glycoproteins CP2 and ZP3 on zona pellucida triggers the acrosome reaction. Describe it.
Mediated by changes in pH that allow Ca2+ to enter acrosome, starts a signalling cascade and flagella start moving
What does the sperm bind to once it has penetraed the zona pellucida?
Oolemma (cytoplasm of oocyte) then it is engulfed
List 4 things that occur when oocyte is activated (when sperm has penetrated).
Cortical reaction to block against other sperm cells takes place
• Ca2+ causes cortical granules to release its contents which changes the structure of the ZP proteins
Activation of egg metabolism (via Ca2+)
Reactivation of meiosis
DNA synthesis
Which protein drives the process of egg activation in fertilisation?
Phospholipase C zeta (PLC-zeta)
Sperm introduces PLCzeta from its cyoplasm into oocyte
What happens when phospholipase C zeta is introduced into the oocyte?
It cleaves PIP2 into IP3 which triggers a cell signalling cascade that result Ca2+ release
The calcium ions break down the protein complex (MPF) that is responsible for maintaining oocyte arrest
• MPF = maturation/meiosis promoting factor
The calcium transience also causes the release of the components in cortical granules
The cortical granule component release changes the structure of the zona pellucida (ZP)
Zinc atoms are released during activation
Around 4 to 8 cell-stage, DNA of embryo is wiped clean of any epigenetic marks. How?
Demethylation + remethylation
What is the role of chorionic gonadotrophin and where is it produced from?
- Chorionic gonadotrophin (hCG) production from embryo sustains pregnancy in the first trimester (then levels fall)
- hCG binds to LH receptors on luteal cells + ensures P4 production
Normal human pregnancy week?
37-42 weeks (40 average)
What does the umbiliac cord develop from?
Connecting stalk
What does the umbilical cord consist of?
o 2 umbilical arteries that carry deoxygenated foetal blood to the placenta
o 1 umbilical vein that carries oxygen + nutrients acquired
o Wharton’s jelly – supporting mucous connective tissue
Which antibodies can cross placental barrier?
IgG
Function of hCG.
Maintains corpus luteum and stimulates foetal thyroid gland
Peaks at day 60-90
Placenta takes over endocrine role eventually so hCG levels fall
The placenta cannot produce oestrogen on its own but oestrogen is needed. How is it produced in pregnancy?
- Mother provides cholesterol
- Foetus converts cholesterol to androgens
- Placenta converts androgens to oestrogens (oestradiol)
Role of oestrogen in pregnancy
Relax pelvic ligaments + increase elasticity of symphysis pubic
Role of progesterone in pregnancy?
Essential in. pregnancy and is an indicator for placental function
Causes decidualization
Increases oviduct/uterine secretions
Reduces uterine contractions
What is quickening?
Feeling baby move
By what week is the foetus larger than the placenta?
17
List the cardiovascular remodelling that takes place in the mother during pregnancy
o Increased blood volume hence increased venous return hence increased atrial size
o Parallel increase in activity by 30-50%
o HR increases by 20%
o SV increases by 20%
o Size of the heart increases by 12%
o Blood pressure remains largely unchanged
Overall effect of respiratory remodelling during pregnancy?
o Respiratory effort increased because total lung capacity decreased
o Vital capacity is maintained but total capacity reduced because residual volume decreased
Respiratory remodelling adaptations during pregnancy.
16-20% more O2 consumed Diaphragm elevated by 4cm Rib cage displaced upwards Breathing becomes thoracic Sensitivity to chemoreceptors is lowered Responsiveness to PCO2 increased • Action of progesterone • Increased tidal volume
How does the renal and urinary systems adapt to pregnancy?
Kidneys enlarge
Increased excretion of waste products
Increased reabsorption of sodium
Increased blood flow + haemodilution
Ureters displaced + enlarged Decreased bladder tone Urinary reflux from bladder to ureters Urinary stasis Richer in glucose and AAs
Increased risk of UTIs
Breast remodelling in pregnnacy
o Stroma increases in bulk
o Lobules increase in size
o Areola darken
o Nipple darkens + becomes more pronounced
o Lactiferous ducts expand + branch for milk delivery
Differentiate between a malformation, deformation and disruption.
- Malformation: primary disturbance of embryogenesis (never going to go right)
- Deformation: late changes in previously normal structures (mechanical effect)
- Disruption: secondary disturbance due to early influence of external factors
Define teratogen.
Teratogen: an agent or factor which causes malformation of an embryo
What does congenital mean?
Present at birth, does not denote aetiology, may/may not be genetic
Which type of congenital defect starts out ok but then goes wrong?
Disruption
- Amniotic bands
- Poland anomaly (interruption of subclavian A.)
Which type of congenital defect was made wrong?
Malformation
Which type of congenital defect was ok but then got squashed?
Deformation
- Poland anomy
- Talipes
- Dislocated hip
Which type of congenital defect is the one problem (malformation/disruption) leading to consequences?
Sequence
The embryoblast (aka pluriblast or inner cell mass) differentiates into which 2 layers?
Hypoblast and epiblast
Mesoderm forms in between
What cell types form amnion?
Ectoderm and mesoderm
What cell types form chorion?
Syncytiotrophoblast and mesoderm
What cell types form the yolk sac?
Endoderm and mesoderm
What does the umbilical cord consist of?
o 2 umbilical arteries that carry deoxygenated foetal blood to the placenta
o 1 umbilical vein that carries oxygen + nutrients acquired
o Wharton’s jelly – supporting mucous connective tissue
The placenta has a transporting and endocrine function. What is transported via the placenta?
o Glucose is transported via GLUT (1, 3, 4, 12)
o Lipids + fats (diffuse freely across placenta)
o Facilitates exchange of respiratory gases
o Waste products excreted from foetus such as: urea, uric acid, creatinine
o Immune cells (IgG)
The placenta has a transporting and endocrine function. What is hormones are made by the placenta?
hCG
Progesterone
Somatomammotropin
Note - OE2 cannot be produced by placenta alone (mother provides cholesterol, foetus converts cholesterol to androgens, placenta converts androgens to oestrogens)
Functions of hCG in pregnancy
Maintains corpus luteum (hence P4)
Peak at 60-90d
Stimulates foetal thyroid gland
Functions of progesterone in pregnancy
Essential in pregnancy
Indicator for placental function
Causes decidualization – changes to endometrial cells in preparation for and during pregnancy
Increases oviduct/uterine secretions
Reduces uterine contractions
Functions of somatomammotrophin in pregnancy
Uncertain role – appears to reduce insulin sensitivity
Secreted from week 5 of pregnancy + rises throughout pregnancy
Functions of oestrogen in pregnancy
x30 higher than normal at week 10
Proliferative effects on mother
Relax pelvic ligaments + increase elasticity of symphysis pubic
Placental cannot synthesis oestrogens from C19 progestogens so C19 androgens are required
• Are synthesised by foetal adrenals, particularly 16-alpha hydroxylated steroids (only occur in foetal liver)
List all the forces of release of pregnancy
Oestrogen – sensitises uterine muscle to oxytocin
Oxytocin from posterior pituitary gland along w/ ADH - stimulates uterine contractions by targeting specific activated receptors in myometrium
Vasopressin (ADH)
Cortisol – decrease progesterone secretion
Prostaglandins – increase myometrium contractility, smooth muscle relaxant at cervical sphincter
Uterine distension – causes increase in contractility of myometrium
CRH – at term increases contractility of myometrium
List all the forces of retention of pregnancy
Progesterone – damps excitability of uterine smooth muscle + strengthens internal os sphincter
Cervix – long tubular structure composed of strong connective tissue (thins down, softens, dilates in labour)
Hypervolemia – extra 40-50% of blood volume inhibits the hormones from the posterior pituitary (oxytocin, ADH)
Adrenaline – sympathetic ns + adrenaline act same was as progesterone + also block oxytocin secretion
Relaxin – Regulates activation of adenylyl cyclase enzyme which is involved in the NG uptake by muscle fibres
During labour which hormone stimulates myometrium to contract more forcefully?
Oxytocin
Uterine contractions occur in waves. Describe true waves
True labour – Uterine contractions are at regular intervals, producing pain, back pain on walking, dilation of the cervix, and show of blood discharge containing mucus
Uterine contractions occur in waves. Describe false waves
False labour (Braxton Hick contractions) – Contractions with no pain on walking etc., no cervical dilation
Which pelvis type if most common in females and most favourable?
Gynaecoid
Which pelvis type is usually found in males and 20% of females (more common in Afro-Caribbean women)?
Android
Define hypertrophy
A. Increase in cell number
B. Increase in cell size
C. Decrease in cell size and number
D. Abnormal cytological appearance and tissue architecture
E. Conversion of one type of differentiated tissue into another
B.t
E.g. muscle
Define hyperplasia
A. Increase in cell number
B. Increase in cell size
C. Decrease in cell size and number
D. Abnormal cytological appearance and tissue architecture
E. Conversion of one type of differentiated tissue into another
A.
E.g. fat
Define dysplasia
A. Increase in cell number
B. Increase in cell size
C. Decrease in cell size and number
D. Abnormal cytological appearance and tissue architecture
E. Conversion of one type of differentiated tissue into another
D.
Dysplasia: abnormal cytological appearance + tissue architecture
Define metaplasia
A. Increase in cell number
B. Increase in cell size
C. Decrease in cell size and number
D. Abnormal cytological appearance and tissue architecture
E. Conversion of one type of differentiated tissue into another
E.
Metaplasia: conversion of one type of differentiated tissue into another
Define atrophy
A. Increase in cell number
B. Increase in cell size
C. Decrease in cell size and number
D. Abnormal cytological appearance and tissue architecture
E. Conversion of one type of differentiated tissue into another
Atrophy: decrease in cell size + number
List the cardinal movements of labour
Engagement (of head into pelvis) Descent Flexion Internal rotation Extension External rotation Expulsion
Which of these are true?
A. Anterior fontanel is big, diamond shaped.
B. Posterior fontanel is much smaller, triangle shaped.
C. Feeling for the sutures and fontanels help determine baby’s position.
All of them
If baby is overdue by ~14 days, which methods would be used to induce labour?
o Oxytocin
o Prostaglandin E – used if cervix is closed
o Amniotomy – used if cervix is open i.e. it’s when you artificial rupture the membranes (break water) (followed by oxytocin for artificial contractions)
o Membrane sweep – stretch cervix which stimulates/irritates it and causes prostaglandins release
o Natural stimulation – emptying bowels and intercourse (prostaglandins in semen)
What is augmentation of labour?
Augmentation is the shortening of labour
Give oxytocin/amniotomy
Some babies only have 1 normal sized lung (pulmonary hypoplasia).
One cause for this is a diaphragmatic hernia.
Explain how this affects the lungs.
Diaphragmatic hernia – allows intestines to enter thorax + compress lungs (so can’t develop)
Pulmonary hypoplasia (incomplete lung development) can be due to Potter’s syndrome.
What is this?
Potter’s syndrome – bilateral renal agenesis –> kidneys don’t produce urine (containing growth factors)
Foetuses inhale this and it helps their lungs grow
What is mammogenesis?
Breast development
It is only fully completed through pregnancy and lactation
What are the stages of mammogenesis?
o Embryonic/foetal – derived from ectoderm + mesoderm layers
o Infancy/childhood – similar for males + females
o Puberty – changes in breasts occur during menstrual cycle because of changing in LH, oestrogen, progesterone
o Pregnancy + lactation – breast dramatically transformed during pregnancy + lactation; structures continue to bud until 35y/o
Complete mammary growth and differentiation requires the action of multiple hormones. List them.
o Anterior pituitary – LH, prolactin (PRL)
o Placental – human placental lactogen (HPL)
o Steroid sex hormones (ovarian, adrenal, placental) – oestrogen, progesterone
What endocrine influence does prolactin have on mammogenesis?
Influences nipple growth
Essential for complete lobular-alveolar development
What endocrine influence does human placental lactogen have on mammogenesis?
Areola growth
What endocrine influence does adrenocorticotropic hormone (ACTH) and hCG have on mammogenesis?
Combine synergistically with PRL and P4 to promote mammary growth
Where are the breasts located (IC space)
Between 2nd and 6th IC space
What are the unicellular milk secreting cells in the epithelial layer of alveoli called?
Lactocytes
What are lactocytes surrounded by?
Supporting structures:
- Myoepithelial cells (smooth muscle contractile cells which propel milk out from alveolus)
- Connective tissue
What percentage of mastitis is infective and what is non-infective?
Non-infective (70%)
Infective (30%)
What does Barlow’s test identify?
Hips which are dislocatable
What does Ortolani’s test identify?
Identifies hips which are dislocated and is used to confirm diagnosis
Describe the Barlow test
o Flex and adduct the hip then gently push the hip posteriorly
o A positive test causes the femoral head to slip out of the acetabulum which you can feel
Desctibe Ortolani’s test
o Gently abduct hip
o If hip is dislocated you can feel, and sometimes hear a ‘clunk’ as the femoral head goes back into the acetabulum during abduction
Summary of when major congenital anomalies occur in the foetus
Neural tube defects (3-16 wks) Heart defects (3-7 wks) Limb defects (4-8 wks) Cleft lip (5-7 wks) Cleft palate (7-9 wks) Malformed ears + deafness (4-9 wks) Eye defects (4-8 wks) Teeth defects (7-16 wks)
22q11 microdeletion
Shprintzen syndrome which is tetralogy of Fallot
Down syndrome
Heart atrioventricular septal defects + reduced tone
Foetal alcohol syndrome
Neurological + craniofacial defects;
Septal defects CAN be found
Turner syndrome
Turner syndrome = coarctation of the aortic
Also: neck webbing and gonadal dysgenesis
Drug of choice for DVT treatment in pregnancy?
Low molecular weight heparin
Williams syndrome
Supravalvular aortic stenosis
