2a. Pregnancy

Question 1

When is there the greatest risk of miscarriage in pregnancy?

Answer 1

The first trimester (0-13 weeks)

Question 2

What is the limit for the survival of a baby outside the womb if born prematurely?

Answer 2

Without the intensive care unit - 27 weeks

With modern day equipment - 23 weeks

Question 3

What are the main maternal changes that take place during pregnancy?

Answer 3

Increased weight [3rd]
Increased blood volume [2nd & later]
Increased blood clotting tendency [2nd & later]
Decreased blood pressure [2nd]

Question 4

What are some additional changes that occur during pregnanacy (usually earlier on)?

Answer 4

Altered brain function [1st & later] – function of the brain changes
Altered hormones [1st & later] – can be largely different to normal physiology
Altered appetite (quantity and quality of what the mother eats changes) [1st & later] – GI imbalance
Altered fluid balance [2nd & later]
Altered emotional state [1st & later]
Altered joints [3rd]
Altered immune system [1st & later]

Question 5

What is the function of Human Chorionic Gonadotrophin in pregnanacy?

Answer 5

Human chorionic gonadotrophin is the key hormone produced by human pregnancy. It is a functional homologue of LH, driving the production of oestrogens and progesterones from the ovaries (drives the corpus luteum).

Question 6

How does HCG keep the pregnancy going and stop a period from occurring?

Answer 6

The corpus luteum degenerates towards the end of the last week of the menstrual cycle. The fall in progesterone results in the breakdown of endometrium. To keep the pregnancy going, we need progesterone. HcG drives the progesterone production from the corpus luteum. It peaks and falls in the first trimester.

Question 7

What is the function of lactogen in pregnancy and how do its levels change?

Answer 7

It modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus
levels increase as the size of the placenta increases.

Question 8

How does the production of steroids (oestrogen/progesterone) change?

Answer 8

For the first couple of months, the corpus luteum produces these hormones. For the next few months, the placenta takes over oestrogen/progesterone production

Question 9

How do the levels of the various hormones change in pregnancy?

Answer 9

hCG shows peak levels in maternal plasma in the first trimester, and declines thereafter
Other main hormones increase as pregnancy progresses
Increases in progesterone, oestrogens and placental lactogen parallel the increased size of the placenta
By 10 weeks gestation, the placenta is the source of all progesterone (up to then, mainly corpus luteum)

Question 10

What are oestrogen and progesterone levels like in a pregnant woman?

Answer 10

Much higher than usual

progesterone (up to 1µM) and estrogens (up to 20nM)

Question 11

What would result in the termination of a pregnancy at any stage?

Answer 11

Low progesterone levels, or administration of a progesterone antagonist
The placenta continuously produces progesterone throughout pregnancy so this does not occur

Question 12

Why is the mother’s endocrine system modified during pregnancy?

Answer 12

Due to high levels of steroids suppressing the HPG, leading to very low levels of LH and FSH throughout pregnancy

Question 13

Define the terms:

• Conceptus
• Embryo
• Foetus
• Inflant

Answer 13

Conceptus – everything resulting from fertilised egg (baby, placenta, fetal membranes, umbilical cord)
Embryo – the developing baby before it is clearly human
Foetus – the baby for the rest of pregnancy – you can now tell it is human
Infant – less precise, normally applied after delivery

Question 14

What is the expected time of delivery and what is this called?

Answer 14

Term (39-40 weeks) is the expected timing of delivery. While this is normally stated as 280 days since the beginning of the last menstrual period (40 weeks), as a medical terminology, ‘term’ covers gestational ages from 37-41 weeks of gestation, with deliveries either side of these limits being ‘preterm’ or ‘post-term’ respectively.

Question 15

What are teratogens?

Answer 15

Agents that cause malformation of an embryo. Especially disrupt development in the early weeks of pregnancy but some vulnerability continues throughout

Question 16

What are the functions of the placenta?

Answer 16

Separation of blood supplies of mother and baby
Exchange of nutrients (maternal to foetal) and waste products (foetal to maternal)
Connection (or anchorage)
Immunoregulation – allows the maternal immune system to switch off, allowing for pregnancy
Biosynthesis (e.g. progesterone, oestrogens and hCG)

Question 17

What are cotyledons and what is their function?

Answer 17

The maternal surface of a placenta is sub-divided into cotyledons (30-60 per placenta). Each cotyledon contains one or more villi, with larger cotyledons containing more villi
The cotyledons receive fetal blood from chorionic vessels and are surrounded by maternal blood, which can exchange oxygen and nutrients with the fetal blood in the capillaries.

Question 18

What is the primary subunit of the placenta?

Answer 18

The placental villus

Question 19

What is each villus made of?

Answer 19

Within each villus there is a complex blood supply, including arterial and venous vessels, connected to smaller capillaries in the terminal portions of each villus. Note that the arterial system contains de-oxygenated blood, and the venous blood is oxygenated - because the placenta has a parallel function to the lungs for the foetus during pregnancy.

Question 20

Outline what happens in a placental villus

Answer 20

The placental villus is extensively branched, which provides a very large surface area
The maternal vascular system is set up over this surface area
Oxygenated blood flows over it and nutrients/oxygen pass into the foetal tissue
Deoxygenated blood flows away (the opposite happens on the foetal side of the villus)
Deoxygenated blood flows in to pick up the oxygen and nutrients, and flows back to the baby

Question 21

How does the placenta develop?

Answer 21

You start off with a very simple linear structure. Then, it grows out sideways and sprouts.
Day 9 post-fertilisation, the conceptus is almost completely implanted within the endometrium
At this stage of development, the outer layer of the conceptus is multinucleated syncytiotrophoblasts
These syncytiotrophoblasts contain fluid-filled lacunae
The underlying layer of cytotrophoblast is proliferating adjacent to the embryo
This is where the placenta will develop.
Following implantation, the cytotrophoblast proliferate into the syncytium
First a columnar structure forms (cytotrophoblast column), which undergoes branching (villous sprouts)
At the centre of each villus are mesenchymal (extra-embryonic mesoderm) cells
From these cells, the villus vascular system develops
The branching process continues through out pregnancy, giving rise to the complex branched villi

Question 22

How does the structure of the placental villus change through pregnancy?

Answer 22

The overall structure of a placental villus does not change throughout pregnancy, but there are modifications. There are fewer cytotrophoblast present at term, so that there can be a closer apposition between the syncytium and the placental capillaries. This will maximise the efficacy of nutrient transfer into the foetal blood, and enhance foetal growth in later pregnancy.

Question 23

What are the two cell types that make up the placenta?

Answer 23

Cytotrophoblasts make up the innner layer

Syncytiotrophoblasts make up the outer layer

Question 24

How are the villi formed?

Answer 24

At the end of the second week, there are small projections of the cytotrophoblast which project into the syncytiotrophoblasts and form primary chorionic villi
At the end of the third week, extra embryonic mesoderm grows into these primary villi forming secondary chorionic villi.
Blood vessels then form inside this and transform them into tertiary chorionic villi

Question 25

How does artery remodelling take place during pregnancy and why is it necessary?

Answer 25

Cytotrophoblast cells block spiral arteries in the uterus
The arteries in the uterus normally have a vascular endothelium and a smooth muscle layer
The ability of the spiral arteries to carry large volumes of blood is limited (due to narrowness)
To get enough nutrients to the baby, it is necessary for these arteries to become wider
Spiral artery remodelling involves loss of endothelium and smooth muscle cells
You end up with distended, non-vasoactive vessels that can carry large volumes of blood at low pressure so more nutrients can be delivered to the baby

Question 26

What is the function of the cytotrophoblast shell in early development?

Answer 26

Limits blood (oxygen) supply to embryo during the first trimester

Question 27

Why is a reduced oxygen supply delivered during the first trimester?

Answer 27

It is thought that the limited oxygen supply means that the amount of free radicals present in the developing embryo is kept low. Less oxygen decreases the change of free radical development

Question 28

When is the blood supply to the fetus increased? Why?

Answer 28

Remodeling of spiral arteries allows high volume blood supply in trimesters 2 and 3 which occurs because this is when infant growth is greatest

Question 29

How is the cytotrophoblast shell formed?

Answer 29

At the earliest stages of pregnancy, the conceptus is in contact with maternal endometrial cells
As it grows, it makes transient contact with the maternal capillaries
But the rapidly proliferating cytotrophoblast cells form a shell around the conceptus
This isolates it from maternal blood by about 4 weeks post fertilisation.

Question 30

What provides the nutrients to the fetus in the first trimester?

Answer 30

The decidual glands hypertrophy during the first trimester of human pregnancy
These provide the nutrients for the placenta and developing baby
The source of the nutrients is (glands: histotrophic) rather than maternal blood (haemotrophic)

Question 31

When does the cytocryptoblast shell remain until?

Answer 31

The cytotrophoblast shell remains in place until about 8 weeks post-fertilisation (10 weeks GA
During weeks 10-12, the cytotrophoblast plugs gradually break down, beginning with those at the periphery of the placenta, and ending with those near the centre.

Question 32

What is the most likely reason for a miscarriage in the late first trimester?

Answer 32

Spiral arteries provide maternal blood to the placenta at this stage, and hence form the main supply of nutrients to the developing placenta and foetus. This is risky: if the placenta isn’t fully anchored to maternal decidua, the increase in pressure as it is exposed to the maternal arterial supply can detach the placenta causing miscarriage.

Question 33

What are the different mal-developments that can occur during pregnancy?

Answer 33

Miscarriage (late first trimester) – if the placenta doesn’t anchor properly
Miscarriage (second trimester)
Pre-eclampsia (high BP and protein in urine) (early delivery)
Fetal growth restriction (small infant)