maternal changes in pregnancy

Question 1

where does the embryo spend its first 6 days?

Answer 1

Fertilisation occurs in the ampulla and the embryo remains there for around six days. This is where it can interact with special secretory cells such as growth factors and transcription factors.

At around six days it is recognised as a blastocyst.

Towards the end of the luteal phase the embryo will begin to see the uterus

Question 2

what happens during day 4 and 5?

Answer 2

Between day four and five is a cell differentiation event forming outer trophoblast cells, inner cell mass and fluid filled cavity (balls of cells difficult to diffuse to centre). Due to the cavity there is a smaller diffusion distance (thus speed).

Trophoblast cells become foetal parts of the placenta and the inner cell mass becomes the foetus itself.

Question 3

describe uterine receptivity

Answer 3

Endometrial changes reach their maximum about seven days after ovulation (day fourteen). The implantation window is six to ten days after the LH spike.
Pre-decidualization occurs nine to ten days after ovulation, decidual cells cover the surface of the uterus.
Decidualization occurs if pregnancy occurs, these cells become modified and filled with lipids and glycogen and the decidua becomes the maternal part of the placenta.
Glandular secretions of endometrium contain GF, adhesion molecules, nutrients, vitamins, matrix proteins and hormones.

Question 4

describe Estrogen and progesterone’s role before, during and after ovulation

Answer 4

Before ovulation the cycle is dominated by oestrogen, which causes proliferation of the endometrium.
At the moment of ovulation the CL is left behind while the egg goes to ampulla.
Progesterone acts on endometrium for more differentiation (i.e. glandular secretions).

Question 5

what happens to the decidual cells on the surface of the endometrium?

Answer 5

Decidual cells on the surface of the endometrium become filled with lipids and glycogen and become the maternal part of the placenta.

Question 6

How does the syncytiotrophoblast result from?

Answer 6

The synctiotrophoblast results from cell fusion (forms a multi-nucleated cytoplasmic mass) and invades the endometrium.

Question 7

what is an autocrine GF for the blastocyst?

Answer 7

Chorionic gonadotropin is an autocrine GF for the blastocyst.

Question 8

describe implantation

Answer 8

Implantation occurs at around day seven to eight where synctiotrophoblasts erode the endometrium. Cells of the embryonic disc separate from the amnion and fluid filled amniotic cavity appears.

A twelve day blastocyst is evident that implantation is complete as extra embryonic mesoderm forms discrete layer beneath cytotrophoblast.

A 16-day embryo show that cytotrophoblast and associated mesoderm have become the chorion and chorionic villi are extending. Lacunae filled with maternal blood mingle with villi.

Question 9

describe placentation

Answer 9

In around four to five weeks the 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.
At thirteen weeks the amniotic sac has filled with extra embryonic coelom. Yolk sac becomes a small pear shaped opening into the digestive tube via vitelline duct.

Question 10

what is the maternal-foetal interface like?

Answer 10

• Maternal arteries and maternal veins and lacunae
• The chorionic villi connected to umbilical cord
• Extra embryonic mesoderm differentiates from cytotrophoblast

Question 11

describe the maternal recognition of pregnancy

Answer 11

Human Chorionic Gonadotrophin (hCG has an alpha and beta subunit where beta is the active subunit) is secreted by the synctiotrophoblast and increases rapidly. It is the basis of a pregnancy test. It prevents the death of the CL so the endometrium is not shed and the CL continues to produce oestrogen and progesterone. There is a rapid change in maternal systems in response to the luteal and later placental steroids.

Question 12

give an overview on the maternal adaptation of pregnancy

Answer 12

Causative factors include: High level of steroids and other hormones, mechanical displacement and foetal requirements.
The systems affected include: energy and metabolic balance, respiratory system, cardiovascular system, GI system, urinary system and endocrine system.
To diagnose an abnormality we need to detect changes in the changes (exacerbate a pre-existing condition or uncover a hidden/mild condition).
Hormones that cause the changes include:
- Placental steroids: The placenta takes over from the CL at around week seven and produces progesterone, E2 and E3.
- Placental peptides: hCG, Human Placental Lactogen (hPL) and GH.
- Maternal and Foetal Pituitary Hormones: GH, TH, PRL and CRH.

Question 13

describe placental steroidogenesis

Answer 13

Effects of Progesterone include:

• Decidualisation (changes in the endometrium for implantation)
• Smooth muscle relaxation (uterine quiescence)
• Mineralocorticoid effect (CVS changes)
• Breast development (glands and stroma)

Effects of Oestrogens (E2 + E3):

• Rely on steroids from foetus and maternal adrenals.
• Development of uterine hypertrophy
• Metabolic changes including insulin resistance
• CVS changes
• Increased clotting factor production (haemostasis) in preparation for labour (hypercoaguable state)
• Breast development

Question 14

what is the average total weight gain during pregnancy?

Answer 14

nine to thirteen kilograms. The foetus and placenta account for around five kilograms and fat and protein account for four and a half. Body water contributes one and a half kilograms and the breasts and uterus are one kilogram each.

Question 15

why is there an increased energy output during pregnancy?

Answer 15

There is increased energy output to cope with the increased respiration and cardiac output, increased storage for the foetus, labour and post-natal preparation and there is a gain in fat and protein stores by four to five kilograms. This is achieved by increased consumption and reduced use, laid down in anterior abdominal wall and utilised later in pregnancy.

Question 16

describe the basal metabolic rate (BMR) during pregnancy

Answer 16

Basal BMR rises by 350kcal/day during mid gestation and 250kcal/day late gestation (equivalent to 40g fat for 350kcal). Glucose increases in the maternal circulation in order to cross the placenta.

Question 17

describe what glucose is like during pregnancy

Answer 17

During the first trimester pancreatic cells increase in number raising circulating insulin so more glucose is taken up into tissues thus fasting serum glucose decreases (maternal reserves). During the second trimester placental lactogen causes insulin resistance so less glucose into stores and increase in serum glucose so more can cross the placenta (foetal reserves).

Question 18

describe how water is gained during pregnancy

Answer 18

Oestrogen and progesterone are so high that they act like a mineralocorticoid thus retaining more sodium from the kidneys thereby increasing blood volume. Renin is produced by the placenta (RAAS) and oestrogen up regulates angiotensinogen synthesis by the liver thus increased Angiotensinogen II and aldosterone. Progesterone decreases vasosensitivity thus vasoconstriction is resistant in women despite high Angiotensinogen II. Connective tissue and ligaments take on water and become a bit softer and there is a decreased thirst threshold and oncotic pressure due to the reset of osmostat all leading to total water gain of eight and a half litres.

Question 19

describe how oxygen consumption is increased during pregnancy

Answer 19

• Oestrogen and progesterone increase respiratory centre sensitivity to CO2= woman breathes deeper
• Also have a change in thoracic anatomy (ribcage is displaced upwards and ribs flare outwards).

High oxygen and low CO2= perfect (As want to give oxygen to foetus and remove CO2 from foetus) = increased gradient from maternal to foetus
- Baby has foetal hb= higher affinity for O2 than adult hb too
- By 6 weeks old= don’t have a lot of foetal hb

Question 20

what is maternal blood like?

Answer 20

• Plasma volume increases by 45%
• Red cell mass increases by 18%= oxygen carrying capacity is higher
• This makes it seem that red blood cells have gone down/anaemic due to increased plasma volume increase but that is not the case
• Increase in white cells and clotting factors, blood becomes hypercoagulable - increased fibrinogen for placental separation, but increased risk of thrombosis.
  Thus if pregnant don’t go long haul flights/immobilised for long period of time= likelihood of thrombosis

Question 21

how is the mother’s cardiovascular system altered during pregnancy?

Answer 21

CO = BP/TPR
CO = HR x SV
The expanding uterus pushes the heart thus changes in ECG and heart sounds are apparent.
Peripheral vasodilation is mediated by endothelium dependent factors such as NO synthesis up regulated by E2 decreasing TPR thus co increases.
Increased cardiac output occurs also due to increased HR (8-10bpm) but primarily SV begins as early as three weeks to max forty per cent at twenty-eight weeks. BP decreases in the first two trimesters.
Extra work may exacerbate pre existing conditions.
Increased CO and vasodilation by steroids reduce peripheral resistance and also increase the flow to the uterus, placenta, muscle, kidney and skin. Neoangiogenesis occurs.
Pregnancy is characterised by low pressure and high blood volume flow.

Question 22

what is the gastrointestinal tract like during pregnancy?

Answer 22

Steroids effect appetite and thirst, reduce GI motility and relax lower oesophageal sphincter thus leading to constipation and acid reflux (also caused by the large uterus). Small frequent meals may combat this.

Folic acid is involved in DNA production and the growth of blood cells which is essential for the uterus, placenta and foetus thus is supplemented during pregnancy as a deficiency can lead to birth defects such as spina bifida (neural tube defects).

Question 23

what is the urinary system like during pregnancy?

Answer 23

• 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 mediate vasoconstriction leading to further vasodilation and increased renal blood flow and increased GFR
• Dilation and relaxation of the bladder and ureters= can persist UTI
• Vasodilation and increased blood flow to kidney= increased filtration rate—> increased clearance of creatinine, urea, uric acid, glucose re-absorption, less effective.

Kidney function tests will look unusual e.g. may see glucose in urine as glucose reabsorption less effective

Question 24

what do placental CRH and cortisol do?

Answer 24

CORTICOTROPHIN RELEASING HORMONE (CRH):

• CRH from placenta and hypothalamus of baby
• 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 release/availability in uteroplacental tissues to activate blood flow, uterine contractions & cervical ripening.
• Prostaglandin effects usually inhibited by progesterone until labour (placental biological clock)

CORTISOL

• Metabolic changes (insulin resistance)
• Foetal lung maturity
• Mineralocorticoid action (aldosterone)

Question 25

describe 2 important placental proteins and what they do

Answer 25

Human Placental Lactogen (hPL) is present only during pregnancy, maternal serum levels rising in relation to the growth of the foetus and placenta. Maximum levels are reached near term. They exhibit similar activities to GH and contribute to metabolic changes like insulin resistance, decrease glucose utilisation and increase in lipolysis. It also has a possible role in lactation due to the cross reactivity with PRL receptors.

Prolactin (PRL) increases throughout pregnancy. Suckling triggers a reflex increasing its production, it is inhibited by progesterone. It has inhibitory action on ovaries post partum causing anovulation and reduces chances of pregnancy again for the first three to sixth months but this is not totally effective.

Question 26

what is the thyroid gland like in a pregnant woman?

Answer 26

Increased production of thyroid hormones to meet increased metabolic demand of pregnancy thus risk of gestational thyrotoxicosis. Increased excretion of iodine and increases absorption of iodine from the gut. If the patient has a history of hyperthyroidism they may require endocrine management using T4 to maintain normal function. Biochemical tests may indicate hyperthyroidism in pregnancy despite it being euthyroid. Suppressed TSH may indicate gestational thyrotoxicosis and HCG may act on the TSH receptor.

At twelve weeks gestation the uterine fundus may be palpated through the abdomen above the symphysis pubis. There is a large increase in muscle mass during the first twenty weeks. After this stretching and increase in blood flow the size reaches its peak at thirty-six weeks.

Question 27

describe the changes to the cervix during pregnancy

Answer 27

The changes to the cervix (retain pregnancy) are an increased vascularity, softening of tissue (connective tissue changes and gradual preparation for expansion) from eight weeks and proliferation of glands (increase in mucus production for protection). Stretching the uterus and cervix during childbirth and stimulation of nipples during breastfeeding cause release of oxytocin from the posterior pituitary, this helps with birth, bonding with the baby and milk production.

Question 28

what happens after birth?

Answer 28

After birth there is a 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; however, never returns to pre-pregnancy size. The removal of steroids permits action of raised PRL on breast.