Pregnancy Flashcards
Where does fertilisation occur?
Ampulla of the uterine tube
The uterine isn’t just a passive tube
It has lots of secretory cells and growth factors that helps the sperm travel to the uterus
When does fertilisation occur?
Around day 4/5
What are two cell types of a fertilised embryo ( blastocysts)?
- Blastocoele fluid-filled
- Inner cell mass forms the fetus
When do endometrium changes reach maximum?
About 7 days after ovulation , if there is no fertilisation after this time progesterone levels drop , endometrium becomes thinner.
How many days after ovulation does decidual cells cover surface of uterus (pre decidualisation?
9-10 days
When does decuidalisation occur?
If pregnancy occurs , decidual cells are modified and become filled with lipids and glycogen. Decidual becomes maternal part of the placenta
What do the glandular secretions of endometrium contain?
Growth factors, adhesion factors, adhesion molecules, nutrients, vitamins, matrix proteins and hormones
Outline the process of uterine receptivity
- Endometrial changes reach their maximum about 7 days after ovulation. The implantation window 6-10 days after the LH spike
- pre decidualisation 9-10 days after ovulation decidual cells cover surface of uterus
- Decidualisation if pregnancy occurs, decidual cells are modified become fluid filled with lipids and glycogen. Decidual becomes maternal part of the placenta.
- Granular secretions of endometrium contains growth factors, adhesion molecules, nutrients, vitamins, matrix proteins and hormones
Decidual cells on surface of endometrium…..
-trophoblast cells project into the endometrial storma.
-syncytiotrophoblast results from cell fusion (forms a multi-nucleated cytoplasmic mass)and invades the endometrium
-chorionic gonadotropin = an autocrine growth factor for blastocyst
Implantation
Implanting day 7-8
1. syncytiotrophoblast erodes the endometrium. Cells of the embryonic discs form epiblast and hypoblast. -Epiblast develops fluid filled amniotic cavity
2. Implantation complete as extra embryonic mesoderm forms discrete layer beneath cytotrophoblast (day 12 blastocyst
-16 day embryo cytotrophoblast and associated mesoderm have become the chorion and chorionic villi are exts
stages of implantation
1.ovulation
2.fertilisation
3. cleavage
4.morula
5.early blastocysts
6.late blastocysts
maternal fetal interphase…
The placenta , where the fetus and mother are connected
Maternal recognition of pregnancy
Human chorionic gonadotrophin (hCG) secreted by syncytiotrophoblast increases rapidly and is the basis of pregnancy test.
hCG prevents the death of the corpus luteum so the endometrium is not shed.
The corupus luteum continues to produce steroids ; estrogen and progesterone which keep the endometrium healthy to hold pregnancy.
Rapid change in maternal systems in response to luteal and later placental steroids
hCG concentration
High in the early stages of pregnancy = pregnancy related complications occur in the first few weeks = bio marker to monitor ectopic pregnancy and other complications
placental steroidogenesis : progesterone
- Synthesised directly from cholesterol
- Decidualization (CL)
- Smooth muscle relaxation – uterine quiescence
- Mineralocorticoid effect – cardiovascular changes
- Breast development (glands and stroma)
placental steroidogenesis :Estrogens
- Synthesised from steroids derived from foetal and maternal adrenals bc Placenta lacks 17α-hydroxylase & 17,20 lyase.
- Development of uterine hypertrophy
- Metabolic changes (insulin resistance)
- Cardiovascular changes
- Increased clotting factor production (haemostasis)
- Breast development (glands and stroma).
Average total weight gain 9-13kg
Foetus and placenta = 5 kg
Fat and protein = 4.5 kg
Body Water (excluding that in other listed structures)
-1.5 kg intravascular
interstitial
intracellular
Breasts 1 kg
Uterus 0.5 - 1kg
About 2.0 kg in total in the first 20 weeks
Then approximately 0.5 kg per week until full term at 40 weeks
A total of 9 -13 kg during the pregnancy.
Failure to gain or sudden change requires investigation.
Constant weight monitoring can cause anxiety.
basal metabolic rate
rises by:
350 kcal/day mid gestation
250 kcal /day late gestation
75% foteus and uterus , 25% respiration
9 calories = 1g fat, therefore 40g fat for 350kcal
glucose increases in the maternal circulation in order to cross the placenta = gestational diabetes
Glucose - 1st trimester (Maternal reserves)
Pancreatic cells increase in number raising circulating
insulin so more glucose is taken up into tissues. Fasting serum glucose decreases.
Glucose - 2nd trimester (Foetal reserves)
Placental Lactogen = insulin resistance, ie less glucose into stores and increase in serum glucose.
this is why some women have gestational diabetes
transfer of glucose to foetus
Increased glucose level in blood during 2nd trimester.
Glucose is transported across placenta as foetal energy source. Foetus stores some in liver.
Total water gain
Estrogen and progesterone are so high that they act like mineralocorticoids….retain more sodium from kidneys thereby increasing blood volume.
RAAS - placental renin production: Estrogen upregulates angiotensinogen synthesis by liver leading to increased angiotensin II and aldosterone. Despite higher ANGII women resistant to AT2 receptor mediated vasoconstriction because progesterone , decreases vasosensitivity = vasoconstriction would lead to FGR bc less substances transferred from mother to fetus via placenta = fatal
Connective tissue and ligaments take on water and become a bit softer.
Resetting osmostat, decreased thirst threshold.
Decrease in oncotic pressure (albumin).
=> up to 8.5 litres total water gain
Oxygen consumption increased
-increases respiratory centre sensitivity to CO2
- thoracic anatomy changes ribcage is displaced upwards and ribs flare outwards
=> breathe deeply -> minute volume increases 40% > arterial pO2 increases 10% ->pCO2 decreases 15-20% which facilitates gas transfer from mother to foetus
Maternal blood
-maternal plasma volume increases by 45%
-red cell mass increases by 18%
=> which increases the efficiency of iron absorption from gut and hemodilution apparent anemia bc Hb conc falls (bc plasma volume is increased from 4.5L to 6L)
=>increase in white cells and clotting factors, blood becomes hypercoaggulated, fibrinogen for placental separation, but increased risk of thrombosis.
Cardiovascular system
- Expanding uterus
pushes heart changes ECG and heart sounds
2.Peripheral vasodilation
mediated by endothelium dependent factors such as nitric oxide synthesis upregulated by E2
20-30% fall in TPR so CO increases…
- Increased cardiac output
increased heart rate (8-10bpm) but primarily stroke volume begins as early as 3 weeks to max 40% at 28 weeks BP decreases in 1st 2 trimesters.
=>Extra work exacerbates pre-existing heart conditions, eg aortic valve defects, pulmonary hypertension.
Cardiovascular system - vessels
Increased cardiac output and vasodilation by steroids- E+P
Reduced peripheral resistance and increased flow to:
Neoangiogenesis, including extra capillaries in skin (spider naevi) to assist heat loss.
Pregnancy characterised by low pressure and high blood volume.
=> CO = BP/TPR
=> CO= HR xSV
GI tract
steroid causes :
-appetite and thirst
- reduced GI motility => constipation
-relaxed lower oesophageal sphincter => acid reflux
-large uterus (expanding)
Dietary supplementation - folic acid
-Supplementation advised up to 400μg/day until week 12.
Ideally 3 months before pregnancy.
Deficiency can lead to birth defects eg spina bifida (neural tube defects).
Urinary system
increased filtration rate = increased clearence of creatinine, urea, uric acid , glucose reabsorbtion less effective
-Relaxin from corpus luteum/placenta stimulates formation of endothelin which mediates dilation of renal arteries by nitric oxide synthesis.
-Progesterone and VEGF cause resistance to angiotensin II mediated vasoconstriction leading to further vasodilation and increased renal blood flow and increased GFR.
urinary frequency
increases
thirstier than normal
high blood volume
increased filtration rate
urethra relaxed
placental CRH and oestrogen production
CRH:
CRH released into maternal and foetal
circulation by placenta. Increases cortisol
(positive feedback) and stimulates
adrenocorticotrophic hormone (ACTH) &
so DHEA in foetal HPA axis.
DHEA (androgen) is aromatized into estrogen
by the placenta. Increasing E:P ratio
and stimulating prostaglandins
which activate blood flow, uterine
contractions & cervical ripening.
placenta cant make eostrogen directly it has to make it by aromatisation.
=>This is one of the things that triggers labour
Cortisol and E2
Cortisol:
-adrenal gland produces cortisol which feedbacks on the placental to increase CRH which stimulates ACTH so DHEA and then aromatisation occurs changing E: P ratio.
-metabolic changes (insulin resistance).
- Foetal lung maturity
- mineralocorticoid action (aldosterone)
-increased prostaglandin E2 and oxytocin production by placenta.
-cortisol helps foetal lung maturity
-surfactant distrupts hydrogen bonds, reduces surface tensions and opens up alveoli
thyroid gland
-increased production of thyroid hormone to meet increased metabolic demand of pregnancy leads
to a risk of gestational thyrotoxicosis, hCG may act on TSH receptor.
If patient has a history of hyperthyroidism such as Graves disease they may require endocrine management to maintain normal function.
Biochemical tests may indicate hyperthyroidism in pregnancy where in fact the patient is normal (euthyroid).
Symptoms can include anxiety, tremor, heat intolerance, palpitations, weight loss or lack of weight gain, goiter, tachycardia, and hyperreflexia but usually associated with persistent vomiting of hyperemesis gravidarum.
Suppressed TSH and high serum T4 may indicate gestational thyrotoxicosis.
=>The major form is thyroxine (T4), which has a longer half-life than triiodothyronine (T3). T4 is converted to the active T3.
uterus hypotrophy
At 12 weeks gestation the uterine fundus may be
palpated through the abdomen above the
symphysis pubis.
Large increase in muscle mass during
first 20 weeks (50g – 1000g).
After this stretching & increases in blood
flow; size reaching a peak at 36 weeks.
size of a pear => watermelon
Changes in cervix
Primary function is to retain the pregnancy
Increase in vascularity
Tissue softens from 8 weeks
changes in connective tissue
begins gradual preparation for expansion
Proliferation of glands
mucosal layer becomes half of mass
great increase in mucus production
Protective ie anti-infective
prolactin
High circulating concentrations of estrogen and progesterone increase prolactin levels during pregnancy.
Part of a family with human placental lactogen and growth hormone – all have widespread metabolic effects.
During pregnancy prolactin is produced by myometrium and placenta, in addition to the pituitary.
Estrogen and progesterone inhibit the stimulatory effects of prolactin on milk production.
The abrupt drop in estrogen and progesterone levels following delivery allow prolactin to induce lactation.
After birth, sucking activates nipple mechanoreceptors signaling the hypothalamus and causing anterior pituitary prolactin secretion.
oestrogen and progesterone inhibits prolactin inducing lactation but the major drop in E and P after birth is what induces prolactin to cause lactation.
Oxytocin
Stretching of uterus and cervix during childbirth causes release of oxytocin which helps with the birth and emotional bonding with the baby.
Suckling stimulus triggers the release of oxytocin from the posterior pituitary gland, which triggers milk ejection.
Prolactin controls milk production (lactogenesis) but the milk-ejection reflex is due to oxytocin.
after pregnancy : return to normal
Dramatic and rapid fall in steroids on delivery of the placenta.
Most endocrine-driven changes return to normal rapidly.
Uterine muscle rapidly loses oedema but contracts slowly: never returns to pre-pregnancy size.
Removal of steroids permits action of raised prolactin on breast.
