Maternal changes in pregnancy

Question 1

Describe the structure of the human blastocyst

Answer 1

The inner cell mass forms the foetus

The trophoblast forms the placenta (on the surface)

The blastocoel forms the fluid filled cavity

Question 2

Describe changes in endometrial receptivity over the cycle

Answer 2

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.

Question 3

Implantation stages

Answer 3

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.

Question 4

Placentation stages

Answer 4

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.

Question 5

What is the process for maternal detection of pregnancy

Answer 5

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.

Question 6

Explain the roles of progesterone and oestrogen in placental steroidogenesis

Answer 6

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)

Question 7

Average total weight gain in pregnancy

Answer 7

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.

Question 8

Describe the basal metabolic rate

Answer 8

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.

Question 9

Glucose stores in pregnancy

Answer 9

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.

Question 10

What causes water gain during pregnancy

Answer 10

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

Question 11

How is oxygen consumption increased during pregnancy

Answer 11

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%

Question 12

Maternal blood

Answer 12

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

Question 13

Changes in cardiovascular system during pregnancy

Answer 13

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.

Question 14

Effect of pregnancy on the GI tract

Answer 14

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

Question 15

Effect of dietary supplementation of folic acid during pregnancy

Answer 15

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).

Question 16

Effect of pregnancy on the urinary system

Answer 16

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

Question 17

Placental cortisol and CRH

Answer 17

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).

Question 18

Effect of placental proteins

Answer 18

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.

Question 19

Effect of pregnancy on the thyroid gland

Answer 19

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

Question 20

Uterine hypertrophy

Answer 20

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.

Question 21

Describe changes in the cervix

Answer 21

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

Question 22

How does everything return to normal

Answer 22

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