Maternal changes in pregnancy

The inner cell mass forms the foetus The trophoblast forms the placenta (on the surface) The blastocoel forms the fluid filled cavity

Endometrial changes reach their maximum about 7 days after ovulation. The implantation window 6 – 10 days after the LH spike. Pre-decidualizaton 9 to 10 days after ovulation decidual cells cover surface of uterus. Decidualization if pregnancy occurs, decidual cells (modified become filled with lipids and glycogen. Decidua becomes maternal part of the placenta. Decidual cells on surface of endometrium become filled with lipids and glycogen- becomes maternal part of the placenta. Glandular secretions of endometrium contains growth factors, adhesion molecules, nutrients, vitamins, matrix proteins and hormones. The syncytiotrophoblast results from cell fusion (forms a multi-nucleated cytoplasmic mass) and invades the endometrium. Chorionic gonadotropin is an autocrine growth factor for the blastocyst.

Implanting day 7-8 Syncytiotrophoblast erodes the endometrium. Cells of the embryonic disc separate from the amnion and fluid filled amniotic cavity appears. 12 day blastocyst Implantation complete as extraembryonic mesoderm forms discrete layer beneath cytotrophoblast. 16 day embryo Cytotrophoblast and associated mesoderm have become the chorion and chorionic villi are extending. Lacunae filled with maternal blood mingle with villi.

4-5 weeks Yolk sac relinquishes its role in vitelline circulation and nutrition. The embryo is nourished via the umbilical vessels that connect to the placenta via the umbilical cord. 13 weeks Amniotic sac has filled extraembryonic coelom. Yolk sac becomes small pear-shaped opening into the digestive tube via vitelline duct.

uman chorionic gonadotrophin (hCG) secreted by the syncytiotrophoblast increases rapidly and is 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. Rapid change in maternal systems in response to luteal and later placental steroids Serum hCG maximal by 9 – 11 weeks. Useful for monitoring early pregnancy complications e.g. ectopic pregnancy or miscarriage.

Progesterone Decidualization (CL) Smooth muscle relaxation – uterine quiescence Mineralocorticoid effect – cardiovascular changes Breast development (glands and stroma) Estrogens - Estradiol (E2), Estriol (E3) Rely on steroids from foetus and maternal adrenals Development of uterine hypertrophy Metabolic changes (insulin resistance) Cardiovascular changes Increased clotting factor production (haemostasis) Breast development (glands and stroma)

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.

Rises by: 350 kcal/day mid gestation 250 kcal/day late gestation (75% foetus 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.

Increased level in blood during 2nd trimester. Actively transported across placenta as foetal energy source Foetus stores some in liver. First trimester Maternal reserves Pancreatic cells increase in number raising circulating insulin so more glucose is taken up into tissues. Fasting serum glucose decreases. Second trimester Foetal reserves Placental Lactogen causes insulin resistance, ie less glucose into stores and increase in serum glucose. More glucose crosses the placenta.

Oestrogen and progesterone are so high that they act like mineralocorticoid….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. Connective tissue and ligaments take on water and become a bit softer. Resetting osmostat, decreased thirst threshold. Decrease in oncotic pressure (albumin). Overall increases water by 8.5L

Causes mother to breathe more deeply: Increases respiratory centre sensitivity to CO2 Thoracic anatomy changes ribcage is displaced upwards & ribs flare outwards Minute volume increases 40% Arterial pO2 increases 10% pCO2 Decreases 15-20%

Maternal plasma volume 45% increase Red cell mass 18% increase Increased efficiency of iron absorption from gut. Haemodilution apparent anaemia as concentration of Hb falls Non-pregnant range Hb 12 - 16g/dl Pregnant range Hb 10.5 - 13g/dl Circulating volume increases from 4.5l to 6l

Expanding uterus pushes heart changes ECG and heart sounds 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 conditions, eg aortic valve defects, pulmonary hypertension. Increased cardiac output and vasodilation by steroids. Reduced peripheral resistance and increased flow to: Uterus Placenta Muscle Kidney Skin Neoangiogenesis, including extra capillaries in skin (spider naevi) to assist heat loss. Pregnancy characterised by low pressure and high blood volume.

Steroids such as oestrogen and progesterone have an impact on appetite and thirst reducing GI motility- causing constipation Relaxed lower oesophageal sphincter + increased size of uterus - causing acid reflux

folic acid causes DNA production causing growth of red blood cells having an impact on the uterus, placenta and foetus 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).

Dilation of the urinary tract occurs increasing chance of UTI Increased blood flow in the kidney due to higher cardiac output means increased filtration rate 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

CRH effect- Released into maternal and foetal circulation by placenta. Possibly involved in labour initiation (placental biological clock). Released into maternal and foetal circulation by placenta. Possibly involved in labour initiation (placental biological clock). CRH leads to increased levels of ACTH and then dehydroepiandrosterone (DHEA) which increases prostaglandin availability in uteroplacental tissues to activate blood flow, uterine contractions & cervical ripening. Cortisol effect: Metabolic changes (insulin resistance). Foetal lung maturity Mineralocorticoid action (aldosterone).

Human placental lactogen (hPL) Present only during pregnancy, maternal serum levels rising in relation to the growth of the foetus and placenta. Maximum levels reached near term. Similar activities to growth hormone. Metabolic changes – insulin resistance, decrease glucose utilisation, increase lipolysis. Possibly some role in lactation – cross reactivity with prolactin receptors. Prolactin Increases throughout pregnancy. Suckling triggers a reflex increasing prolactin production – inhibited by progesterone. Has inhibitory action on ovaries post partum causing anovulation and reduces chances of pregnancy again for the first 3-6 months - not totally effective.

Increased production of thyroid hormone to meet increased metabolic demand of pregnancy leads to a risk of gestational thyrotoxicosis 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). Suppressed TSH may indicate gestational thyrotoxicosis. hCG may act on TSH receptor. The major form is thyroxine (T4), which has a longer half-life than triiodothyronine (T3). T4 is converted to the active T3

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.

Primary function is to retain the pregnancy Increase in vascularity Tissue softens and turns bluer 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

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