RDA; Lecture 1, 2 and 3 - Complexity of Labour, Embryology and Child development Flashcards
What is the difference between the gestational age and post-fertilisation?
- Gestational age starts from the first day of the last period;
- post-fertilisation is 2 weeks less than gestational age -> makes a difference at the beginning of the pregnancy, but not really at the end of the pregnancy.
Difference between IVF gestational age and non-IVF GA (around 2/2.5wks) -> important as it can change whether the baby will be resuscitated or not (24 vs 22 wks)
What are the main size gains that occur in each trimester?
Last 2 trimesters are for growth of foetus, but first trimester is for development
What are the carnegie stages of human development?
x
What occurs in the first trimester?
x
How are the carnegie stages broken up into weeks of pregnancy?
x
What is the difference between a blastocyst, embryo and foetus?
Red area is the liver as the RBC are produced in the liver in the embryo as there is no bone marrow, yolk is used for nutrition -> very translucent. Embryo is baby up to week 8, foetus is baby for rest of pregnancy
What is a conceptus?
Everything produced from a fertilized egg
What is an embryo?
Cells that give rise to everything at the beginning not just the baby -> terms are used in 2 different ways; baby up to week 8 of development OR for the first week then whole conceptus is embryo, after blastocyst differentiation, then only baby tissue is foetus
Why does cell proliferation occur?
Changes in response to ‘growth factors’
Changes in receptor expression
May be due to changes in cell survival
All paracrine or autocrine regulation
Why do cells move?
Chemo-attractants (local production, paracrine effects), cognate receptors (expressed on target cells) -> needs facilitation, requiring change in tissue structures; remodelling of tissues (ECM) and proteases and inhibitors need to be produced and activated
What are the steps of differentiation that occur in foetus?
Paracrine regulation
Receptor expression
Necessary in target cells
Loss of proliferation
Not necessarily in embryo or fetus
Cells can differentiate and proliferate at the same time
How does cell loss occur in foetus?
Apoptosis -> regulated cell death, controlled by paracrine factors mainly
How can concentration of paracrine stimulus affect regulation of cells?
Some cells exposed to different regulators and different concentrations, which by working together can bring out how cells behave -> occurs in 3D (shown here in different planes) and looks like a limb bud (occurs in embryo proliferation)
How can different regulators work together in the embryo?
x
How do genetic factors regulate development?
Controlled by signals from genes.
Complex gene interactions occur throughout development to form a normal fetus.
Hox genes, with retinoic acid controlling activation of Hox genes
What does embryonic development need?
Gradients of factors
Combinations of factors
Temporal changes in factors or responses to them
What is the bilaminar disc (~9d PF)?
Epiblast (yellow) and hypoblasts (blue) -> circular disc cut in the middle
What is gastrulation?
Becomes more elongated -> Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar (“three-layered”) structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.
How is the germ layer formed?
Proliferating and differentiating to form mesoderm cells, which move towards the hypoblast -> forming the germ layers; hypoblast is bumping into mesoderm cells which then undergo another differentiation stage, forming the endoderm, with hypoblast being lost via apoptosis
What does gastrulation result in?
Epiblast becomes ectoderm, mesoderm is in the middle, endoderm is where the hypoblast was
What do the 3 germ layers become?
NB: very few tissues are of one specific type -> skin is both ectoderm and mesoderm
What is neurulation?
Occurs at the same time as gastrulation -> can see the primitive streak;
Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube.
The embryo at this stage is termed the neurula.
Notochord (acts as negative regulator, not allowing certain things to happen) formed from mesoderm, and upper epiblast layer is turning into neural plate which forms the CNS.
Proliferation cells, grow and meet in the middle forming the neural tube which will then become the CNS. Skin overlies the CNS, which explains why some neuroblastomas can affect the skin as well as the NS, as they have the same embryological origin.
By day 21, 3D embryo is developing, with mesoderm becoming more dimensional
How does the body cavity close?
Umbilical cord is a gap in the body wall, where the yolk was
How does the embryo fold head to tail?
x
What occurs in the 2nd month of development?
Faces developing, hands developing, eyes developing from an early stage; apoptosis used to remove webbing in between fingers and remove our tail
When do each of the systems develop?
x
How does the CNS develop?
Brain development occurs in 2 separate halves -> with fusion of tissues and elaboration occurs -> neuropores then fuse to give a complete tube that is the CNS
What is spina bifida?
Twin/two spines, with 2 areas of tissue -> bulges of tissue and depending where they are and what is in them decides the problems that it is going to cause -> above the point is normal;
Incidence of 1-2 per 1000 pregnancies;
Surgery can help anatomical but not functional problems and folic acid (need to take it earlier to have enough reserve for baby) can prevent it, primary problem is failure to complete neurulation and problem is present within 4 weeks of fertilisation
How is spina bifida caused?
A gap is left where the fusion would have occurred -> posterior neural chord hasn’t closed properly
What are the types of spina bifida?
Occulta has a patch of hair, with vertebra not being formed properly; in meningocele is a bulge of CSF; myelomeningocele includes neural tissue and CSF -> development of bones of spine are controlled by neural tissue, which means it doesn’t cut off the neural tissue in spina bifida
What is anencephaly?
- Incidence: 1 – 8 per 10,000 births
- Female babies affected more commonly than male.
- Large part of the skull is absent along with the cerebral hemispheres of the brain.
- Folic acid may show benefit, anterior neuropore closure is incomplete
How does the heart develop?
Blood is flowing through the tubes from the 20d
How do the endocardial tubes moves in developement?
Stay at the sides of the embryo -> heart is being pushed when the embryo is folded
What is the relevance of the secondary heart field?
Joined at the top, and then top point breaks down, with it forming 2 tubes, some formed from primary and some from secondary heart field
How does the heart form from the 2 endocardial tubes?
Rotation of 2 structures -> X left in place but the 2 rotate around each other;
- ventricular structure increases in size,
- and then they continue rotating,
- with the atria rotating behind the ventricles,
- with arteries coming out in front
Why does the heart change in development so much?
Compression of atria causes bending of atrium, which then bends round itself, and bends completely -> more physical force than movement and proliferation
How does the fetal heart look?
Ductus arteriosus makes most of the blood get diverted from the pulmonary artery into the aorta as we don’t need our lungs until birth -> blood flows from body to heart to body
What changes occur at birth to the heart?
x
How do the limbs develop?
x
What is achrondroplasia?
Gain of function mutation of FGFR3
What is thalidomide?
Didn’t directly interfere with FGF8 (apical ectodermal ridge) or Shh (zone of polarising activity), affected vessel formation -> with prolonged exposure leading to widespread cell death and all signalling/cells lost; short exposure leading to uniform cell death and only partial loss of AER signalling which recovers
What is polydactyly?
Extra finger development -> mild developmental defects
How is the kidney developed?
- In early development, early kidney does act as an excretory organ but then can develop into reproductive tract.
- Pronephros: develops first, precursor tissue that directs formation of Mesonephros: which connects to the cloaca. Limited excretory functions
- Metanephros: definitive kidney
- The third urinary organ, the metanephros or permanent kidney appears by the ffth week. Its excretory units develop from the metanephric mesoderm.
- The collecting ducts of the permanent kidney develop from the ureteric bud, an outgrowth of the cloaca.
- The bud penetrates the metanephric tissue and gives rise to the ureter, the renal pelvis, the major and minor calyces and collecting tubules.
- Each newly formed collecting tubule is covered at its end by a metanephric tissue cap form small vesicles which form nephrons.
How do the kidneys ascend?
x
How is the bladder formed?
x
What happens if the development of the kidneys goes wrong?
Renal agenesis
Abnormal shaped kidneys
Abnormal ureter
Pelvic or horseshoe shaped kidney
Bladder exstrophy
What is renal agenesis?
x
What are the abnormal shapes of kidneys?
Pelvic and horseshoe kidneys
What are the ureteric abnormalities?
x
How do the gonads develop?
- The gonads arise from intermediate mesoderm within the urogenital ridges of the embryo
- Primordial germ cells are the precursors of all gametes
- The genital ducts arise from paired mesonephric and paramesonephric ducts
- The mesonephric ducts give rise to MALE genital ducts
- The paramesonephric ducts give rise to FEMALE genital ducts
What is the early urogenital development?
x
How do the ductal systems develop?
Week 7 ->The genital ducts arise from paired mesonephric and paramesonephric ducts
The mesonephric ducts give rise to MALE genital ducts
The paramesonephric ducts give rise to FEMALE genital ducts
How does sexual differentiation occur?
The gonads and reproductive tracts are indifferent up until 7 weeks of development; differentiation is determined largely by the presence or absence of SRY (on the Y chromosome)
Normally: If SRY+, then development proceeds along the male path (~7 weeks onwards)
If SRY-, then development proceeds along the female path (~9 weeks onwards)
How does the male reproductive tract develop?
- SRY expression: a gonad develops into a TESTIS containing spermatogonia, Leydig cells, and Sertoli cells.
- Leydig cells produce TESTOSTERONE, which support growth of the mesonephric ducts.
- NOTE: without testosterone, the mesonephric ducts will regress
- Some testosterone is converted into Dihyroxytestosterone (DHT), which supports development of the prostate gland, penis, and scrotum.
- Sertoli cells produce ANTI-MÜLLERIAN HORMONE (AMH, or Müllerian Inhibiting Substance, MIS), which induces regression of the paramesonephric ducts.
- NOTE: in the absence of MIS, the paramesonephric ducts will persist.
How does the female reproductive tract form?
In the absence of SRY, the gonad develops into an ovary with oogonia and stromal cells.
Since no testosterone is produced, the mesonephric (Woolfian) ducts regress.
Since there is also no AMH (MIS), the Müllerian (paramesonephric) ducts persist to give rise to the oviducts, uterus, and upper 1/3 of the vagina
The urogenital sinus contributes to the formation of the bulbourethral glands and the lower 2/3 of the vagina
What are the female parts and where do they develop from?
- Ureteric bud: ureter
- Mesonephric ducts: trigone of bladder
- Paramesonephric ducts: oviduct, uterus, upper 1/3 of vagina
- Urogenital sinus: bladder (except trigone), bulbourethral gland, urethra, lower 2/3 of vagina
Compare the female and male gonadal development.
x
When do the testes descend?
The testes arise in the lumbar region but then descend into pelvic cavity and through the inguinal canal to end up in the scrotum
Descent of the testis is due to tethering of the testes to the anterior body wall by the gubernaculum.
With growth and elongation of the embryo coupled with shortening of the gubernaculum, the testes are pulled through the body wall, then the inguinal canal, and finally into the scrotum.
Undescended testes are at increased risk of cancers and don’t function normally
How do the external genitalia form?
Male structures form under the control of testosterone.
In the absence of testosterone, female structures will form
What are the abnormal developments of reproductive system that can occur?
Structural (hypospadias M or uterine abnormalities F), others due to changes in hormone production
What are hypospadias?
x
What are mullerian duct anomalies and persistent Mulleria Duct syndrome?
Occurs in genetic males with mutations in AMH / MIS or the AMH / MIS receptor
Because testosterone and DHT are produced, there are normal male external genitalia and male (Wolffian) genital ducts
Because there is no inhibition, the paramesonephric ducts persist; i.e. there is a small uterus and paired fallopian tubes
The testes may lay either in what would be the normal position for ovaries (i.e. within the broad ligament) or one or both testes may descend into the scrotum
What is androgen insensitivity syndrome?
Occurs in genetic males (XY) with mutations in the androgen receptor (AR)
Lack of virilization of due to inability of AR to bind testosterone or DHT, so androgens have no effect
Relatively normal female external genitalia (no functional androgens) but undescended testes
Mesonephric ducts are rudimentary or lacking due to loss of testosterone signaling
Normal production of MIS from Sertoli cells causes Müllerian duct regression, so no oviducts, uterus, or upper 1/3 of vagina.
Errors in production or sensitivity to testes hormones lead to a predominance of female characteristics under the influence of maternal and placental estrogens.
What is congenital adrenal hyperplasia?
x
How does the face develop?
Primary structures of face form on sides of head, until at least 5w post fertilisation ->
precursors of nose, cheeks, lips, mouth and chin also formed during this time period.
Structures move over 5wks to reach expected positions, nose centrally placed and eyes facing forward on face ->
process of movements of preformed structures like eyes isn’t fully understood, but could be continuous formation of clefts in face, then filling in of clefts which leads to subsequential loss of tissue from centre of face and movement of tissues to correct places
What is a cleft lip?
The face hasn’t joined together, usually occurs in the upper lip -> cleft lip is usually asymmetrical but cleft palate is symmetrical usually, as halves of palate don’t meet and fuse correctly -> can be surgically cured, as cell turnover in infants is normally very rapid and healing often occurs with little/no scarring
How do the lungs develop?
Using PF timings -> enough surfactant in around 30 weeks for lungs to expand
How do the lungs develop from week 3-4?
x
How do the lungs develop from week 5-8?
x
How do the lungs develop at a cellular level?
x
What are the cellular components of the mature lung?
x
What is respiratory distress syndrome?
Respiratory distress syndrome (RDS), respiratory distress syndrome of newborn (RDSN), surfactant deficiency disorder (SDD);
previously called hyaline membrane disease (HMD).
Overall incidence
- ~1% of all births
- ~100% at GA 24 weeks
- ~50% at GA 26-28 weeks
- ~25% at GA 30-31 weeks
Time to allow surfactant production to increase
How is surfactant produced during pregnancy?
- Surfactant: lipids, proteins and glycoproteins In utero production can be increased by 1 injection of glucocorticoids (2-3 days)
- Composition:
- ~40-45% dipalmitoyl-phosphatidylcholine (DP-PC)
- ~40-45% other phospholipids, mainly other PC
- ~5% surfactant-associated proteins (SAP or SP-A, -B, -C, -D)
- ~5% other proteins
- Cholesterol
- Trace components
Half life of 5-10h, made by type II cells and lower surface tension in alveoli
What are teratogens?
Factors which dysregulate patterning, causing defects in development -> many different factors can act as teratogens (illegal drugs, meds, radiation, infections) but all exert their main effects in the first trimester of pregnancy
What is the difference between miscarriage, term and preterm?
x
What is labour?
Fundally dominant contractions (push downwards, starting from the top), and cervical ripening and effacement (increasing).
Co-ordinated myometrial contractions (increasing)
Rupture of fetal membranes
Delivery of infant
Delivery of placenta
Contraction of uterus
What are the stages of labour?
Longer in first pregnancy, than the next pregnancies
How do you initiate labour?
Term: Not really sure - Estrogens; low progesterone?; CRH?; oxytocin?
Preterm: Intrauterine infection, Intrauterine bleeding, Multiple pregnancy, Stress (maternal), Others
How does the cervix ripening and effacement occur?
Change from rigid to flexible structure
Remodelling (loss) of extracellular matrix
Recruitment of leukocytes (neutrophils)
Inflammatory process
Prostaglandin E2, interleukin-8
Local (paracrine) change in IL-8
How do the coordinated myometrial contraction occur?
Fundal dominance
Increased co-ordination of contractions
Increased power of contractions
Key mediators
Prostaglandin F2a (E2) levels increased from fetal membranes
Oxytocin receptor increased
Contraction associated proteins
How does the rupture of the fetal membranes occur?
Loss of strength due to changes in amnion basement component Inflammatory changes, leukocyte recruitment
Modest in normal labour, exacerbated in preterm labour
Increased levels and activity of MMPs Inflammatory process in fetal membranes
Summarise the tissues and processes that occur during labour?
x
What is NFkB?
Many genes, mostly ‘inflammatory’: COX-2 (prostaglandins - PGs), IL-8, IL-1b, MMPs, Oxytocin receptor, PG receptors;
contraction-associated proteins are activated by NFkB -> all prolabour genes have NFkB binding domains in promoters
What are the causes of preterm labour?
Inflammatory changes are strongly linked with labour -> activators of inflammation are readily linked with preterm labour
How is term labour controlled?
Constitutive PGE2 synthesis occurs, increasing with labour -> CRH binding proteins increases towards labours, also coinciding with COX2 expression increasing in parallel with CRH; PAF as well signals fetal maturity; IL-1beta also increases during labour
What is platelet activating factor?
Part of lung surfactant, surfactant proteins and complexes -> produced by maturing lung, before birth, with levels in amniotic fluid increasing near term -> sign of fetal maturity
What is the hypothesis for parturition?
Lungs making PAF, driving IL and PGE2 production;
CRH produced in placenta, stimulating ACTH production, which stimulates adrenal gland to make Cortisol and DHEA,
With cortisol going back to the placenta, with cortisol stimulating CRH production, feeding forward and eventually driving labour.
Oestrogens formed from DHEA, which then leads to myometrial contractions
What is progesterone used for in pregnancy?
Needed to sustain pregnancy -> if progesterone blockaed occurs then pregnancy is lost;
progesterone levels remain very high until after delivery of placenta, with effect of progesterone being lost in normal term labour -> lots of progesterone receptors = normal progesterone function;
high NFkB with low progesterone receptor = negative interaction
What happens to the progesterone receptor A and B?
PR-B mediates the main effects of progesterone via gene expression
PR-A is less able to mediate these effects
Ratio of PR-A : PR-B increases at term
Loss or change in PR may lead to ‘functional progesterone withdrawal’
What part of labour is affected by progesterone?
x
What is development?
x
What factors can affect child development?
- Child development is now seen as a bidirectional transactional process in which genetic and environmental influences continuously alter each other in a dynamic manner.
- Various levels of contexts such as parenting, poverty and social networks interact with each other and with genetic expression to create long-lasting consequences for development.
- Environmental factors become even more important determinants of the child’s future in the presence of any biological risk.
- While single or isolated negative environmental factors may have a small, incremental effect, accumulated risk factors make a major contribution to developmental problems.
- Family and social environment most strongly but not exclusively, influences emotional regulation, cognitive and language outcomes, with most negative influence occurring in infancy
What are the environmental causes of damage to brain development both antenatally and postnatally?
x
What are the periods of susceptibility to teratogenesis?
x
Which infectious agents can affect development of the baby?
x
What features can babies develop when the mother gets rubella during pregnancy?
x
What drugs/substances can cause problems with development?
x
Which hormones can cause problems with child development?
Gestational diabetes can give larger babies - >5kg
How can the maternal diet affect the baby?
x
What are the complications of spina bifida?
x
What are the domains of development?
Milestones are the acquisitions of a key performance skill is referred to as a milestone, with normal range varying widely
What are the milestones of movement from newborn to 6-8months?
x
What are the milestones of movement from 8-15months?
x
What are some intermediate steps that can occur when trying to walk?
x
What are the primitive reflexes?
Are protective and have a survival value,
Promote proper orientation,
Promote postural support and balance;
Moro reflexis a grasping motion when dropped slightly;
asymmetric tonic reflex is turning head to one side with that side of limbs extending and opposite side flexing
Which reflexes replace the primitive reflexes after 4-5months ?
Called protective/righting responses
What are the visual milestones from 6 weeks to 7 months?
x
What are the visual milestones from 10 months to 2-5y?
x
What are the language milestones from newborn to 10 months?
x
What are the language milestones from 12 months to 2.5-3y?
x
What are the social milestones from 6 weeks to 12 months?
x
What are the skill milestones during development (summary)?
x
What are the limit ages for certain skills?
x
What are the patterns of delay?
- Slow but steady, plateau, regresses = patterns of delay;
- wide age band across which it can be normal to achieve a developmental skill.
- Limit ages denote beyond normal range.
- The gap between normal and abnormal development becomes greater with increasing age and therefore becomes more apparent over time -> range of normality is very small at the beginning of life with expansion as the years go one.
- Regression = loss of skill which was acquired, with very poor prognosis
What are the causes of delay in development?
x
How do children present with developmental problems?
Have spot checks -> 6-8wk by GP, 9m check by health visitor, 12month check by HCP;
preschool 3y check assessed by doctor;
prematurity can increase RF for ADHD and autism;
What questions should you ask to identify any problems?
- Is there a problem?
- What are the problems?
- What is the extent/impact of the problem?
- What is the cause of the problem?
- What are the comorbidities?
- What can be done?
What are the risks of prematurity with development?
Haemorrhage, periventricular leukomalacia are big problems
How would you carry out a physical examination of the baby for development?
- Use SOGSII (tick what they can achieve, add the number and look at chart to determine skill set),
- Griffiths (looks at skills, with colour coding, testing similar skills and then plot on chart to see achieved centile, takes longer around 1-1.5h), Denver (2 domains)
Which targeted examinations/tests would you carry out for developmental problems?
Don’t need to do all, need to be specific and give time as well -> chromosome test, thyroid test, acids and imaging, hearing and vision assessment
What are the Child Development Services?
x
Summarise the general issues for the child with delayed/abnormal development at a glance.
x
What are other problems of cerebral palsy?
x
Summarise cerebral palsy.
x
What is autism?
x
What are the social symptoms of autism?
x
What is a learning disability?
x
What are the causes of learning disabilities?
x
How can learning disabilities affect education?
x
What is ADHD?
x
How does the hypothalamus and pituitary work together to regulate the pathways in the male reproductive system?
A complex interplay between hypothalamic, pituitary and gonadal factors is needed to control the normal production of human sperm.
What are the key stages of spermatogenesis?
The overall production of sperm from both testes is estimated to up to 200 million sperm per day.
Once the process of spermatogenesis starts (at puberty) it normally continues for the rest of adult life.
The quality and quantity of sperm produced may decline with increasing age, but men are capable of fathering children at well over 70 years of age.
What are the main features of the female reproductive system?
How does oogenesis occur?
The pic shows the changes in follicular structure as they develop and increase in size, but also notes that follicles may not develop all the way to ovulation - atresia is common, as shown.
The thecal cells of the developing follicles are responsible for the production of estrogens, and the granulosa-luteal cells produce estrogens and progesterone during the second half of the ovarian cycle.
What is the menstrual cycle?
Both the ovarian and endometrial cycles have end-points that occur approximately once per month; this superficial similarity disguises some differences that need to be considered if the complexities of oocyte production are to be identified correctly -> lasts approx, 28d but varies between persons, usually between 21-35d in adult females, with younger girls (menarche) = <45d and menopause = skip a month, shorter, longer, irregular
Summarise the hormone regulation during the human menstrual cycle
x
What are the changes in tissue structures that occur during the normal menstrual cycle?
Changes in endometrial thickness during the cycle are shown, as are the roles of estrogen (proliferative or follicular phase) and of progesterone in combination with estrogen (secretory or luteal phase).
Note the terminology used: a focus on endometrial or uterine function will employ proliferative and secretory, as these describe endometrial function; for an ovarian emphasis, the terms would be follicular and luteal, as these summarise the state of the dominant ovarian follicle in the cycle.
Summarise the hormonal changes during the human menstrual cycle
The key changes in the four main hormones are summarised, showing the time-frames of the changes. Note that the basal body temperature rises slightly (about 0.5°C) around the time of ovulation.
How does folliculogenesis occur?
- Time taken for primordial follicle to develop into a secondary oocyte is more than one month;
- Human ovaries contain multiple follicles at all stages with one dominant follicle entering the later stages to form a Graafian follicle;
- usually the ovaries take turns, so each ovary has 56 days to release the secondary follicle.
- Human ovaries contain 2 million primordial follicles at birth but only ~400 are released at ovulation during repro lifetime;
- human oogenesis is intermittent, both 1st/2nd mitotic division are paused during follicle development, with meiosis 1 beginning during embryonic development and halting at diplotene stage of prophase I, persisting until puberty where meisosi resumes as 2ry follicles develop;
- only fertilisation can cause completion of meiosis in an oocyte
What are the main events of fertilisation?
- Deposition of sperm within female system following sexual intercourse.
- Sperm are deposited near cervix
- Cervical mucus is normally hostile to sperm, forming a physical barrier to sperm
- Cervical mucus changes at mid-cycle, allowing sperm to enter uterus.
- 1) Fusion of sperm with egg, ZP digested by enzymes released during sperm capacitation.
- 2) Cortical reaction initiated, leading to herdening of ZP and exclusion of other sperm.
- 3) Meisois II in maternal chromosomes is completed, so polar body II and female pronucleus is formed. Head of sperm is undergoing decondensation, with previously tightly packed paternal chromosomes, forming a much looser structure; both pronuclei are haploid.
- 4) Pronuclei visible, DNA in both has been duplicated; next stage is mitotic division, maternal and paternal chromosomes mix for the first time, as metaphase plate of first cleavage division is formed.
- 5) Separation of male/female chromatids can be seen, and each cell should receive one paternal and one maternal copy.
What are the hormonal changes that occur in pregnancy?
- hCG peaks in maternal plasma in 1st trimester then declines.
- Increase in P, O and lactogen parallel increase in size of placenta (hCG also produced by placenta but regulation is different).
- P and O exceed levels in normal menstrual cycle, so have potent effects on maternal system, with P being key hormone to letting pregnancy continue.
- High negative feedback means very low LH/FSH so no ovarian/uterine functions.
Where does oestrogen come from during the pregnancy?
Early wks = corpus luteum makes O, mainy 17b-oestradiol; once luteo-placental shift occurs, then O made with fetus, and maternal liver/adrenals.
Placenta doesn’t have CYP450, so takes part in fetal adrenals.
DHEA is sulphated into inactive DHEA-S, so female fetus isn’t exposed to androgens during development/ DHEA-S circulates to placenta, converted into 17b-oestradiol;
Oestriol levels are very high produced by parallel mechanis, including OH of DHEA-S in fetal liver into 16OH-DHEA-S
What is the structure of the placenta?
- Primary subunit is the placental villus which has the complex branched structure -> provides large SA for exchange of maternal/fetal vascular systems -> primary requirement for exchange function.
- In each villus, arterial and venous vessels connected to smaller capillaries in terminal portions of villus -> arterial system = deoxygenated, venous = oxygenated.
- Fetal and maternal blood supplies are separated from each other.
- Maternal surface of placenta subdivided into cotyledons which contain one or more villi, larger cotyledons, containing more.
- Variability in shape and size of cotyledons doesn’t affect placenta function
How do you determine externally the size of the fetus?
Determine size by palpation of maternal abdomen, basis of symphysis fundal height -> ID the distance between the pubic symphysis and the top of the uterus -> reflects generic changes in uterine size, its vulnerable to errors
What are the causes of IUGR?
Generally develops in the 2/3rd trimesters, with the first concentrating on the development of embryonic and fetal structures and almost all weight gain occurs later in preg, so main causes are apparent then -> these factors can be combined which increases IUGR
