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What is preeclampsia?

It is hypertension during the second half of pegnancy 3-8% of all pregnancies. 3000 maternal cases in NZ per year. Kills more babies than mothers.

Affects most maternal organs.
Increased protein in the urine.
Triggered by the placenta have to deliver the placenta to fix).

There is an exaggerated inflammatory response leading to vascular dysfunction. Failure of vascular adaption and loss of normal relaxation of the maternal peripheral vascular resistance seen in pregnancy.

Decreased blood flow to the fetus can cause intrauterine growth restriction. It makes it more likely for the baby to be born early, and increases the chance to be stillborn

Increases the risk for the rate of cariovascular deaths in later life.


What are the functions of the placenta?

Self-matienence and renewal.
Transfer of oxygen and nutrients from mother to fetus, transfer of wastes from fetus to mum.
Separation of baby from mum.
Protection of fetus from infections
Protection of fetus from maternal immune system


What is the placenta made up of?

Chorionic villi.


When is the real placenta formed?

Around day 12 of gestation


What are the cells of the placenta?

The trophoectoderm cells of the blastocyst become trophoblasts (multiple types).

The outside surface of the placenta consists of Syncytiotrophoblast. These originate from the polar trophoectoderm, just under the inner cell mass and are the cells that invade into the uterine wall.
Cytotrophoblasts that are sitting further back invade under the syncytiotrophoblasts on the fetal side. These become primary villi.
The gaps between the primary villi are called the intervillous space. This will fill with maternal blood.

At day 14 the extraembrionic mesenchyme invade the primary villi becoming secondary villi.

At about 18-20 days capillaries form in the villi (tertiary villi). The capillaries form here before they form in the embryo.


What happens in the spiral arteries after nidation?

The trophoblasts migrate into the spiral arteries (not veins) and replace the endothelial cells and the smooth muscle (endothelial trophoblasts). The prevent arteries from responding to stimuli that would cause the arteries to constrict, such as a fight or flight response, which would otherwise restrict blood flow to the embryo, which would restrict growth. Growth restriction will cause early birth.
This is coplete within 22 weeks of gestation.

Should go right through spiral arteries and 1/3 of the spiral arteries or radial arteries in the myometrium.

Initially a trophoblast plug is formed, shortly after gestation, in the spiral arteries to protect the embryo in early development. They act like a sieve. Plasma can get through but RBCs can't. Like this for the first 10-12 weeks. It causes low oxygen in the placenta (1%).


What does a growing embryo eat when the spiral arteries are pluged?

Glandular milk. Uterine glands secretion entering the intervilious space (histiotrophic nutrition). When ths blood can get throgh the spiral arteries the feeding is called haemochorial nutrition. This happens when the trophoblast plug breaks down around week 12


What is the association between placenta blood flow and miscarriage?

In miscarriage the placental blood flow occurs earlier than expected (expected breakdown of the trophoblast plug around week 12) and is distributed centrally. Usually it starts from the periphery and causes the sides and back of the placenta to regress.


Define villous?

Branch of the placenta. Makes up the placenta.


Define villous cytotrophoblast?

Trophoblast progenitor found mainly in the first trimester underlying the syncytiotrophoblast. They are the progenitor cells for the synsytotrophoblasts.


Define the synsytotrophoblast.

Single cell layer that covers the entire placenta. It does not proliferate. It does not replicate but are fused to by villous cytotrophoblasts. Sytotrophoblasts do not replicate.


Define extra-villous cytotrophoblast?

Differentiated cells that have migrated out of the villous placenta towards the maternal tissues. Into the spiral arteries. Increases the maternal blood supply to the placenta.


What happens to the placenta as it grows?

In early pregnancy, there is a lot of space between villi and the fetal vessels are deep in the villi.

During the second trimester the villous cytotrophoblasts (not extra villous) thin out as the placenta grows and then becomes sparse.
The branching of the villi increase. Less intravillous space.
The size of the placenta increases.


What are the regions of the decidua called that come into contact with the placenta?

Decidua basalis: the region underlying the implantation site (bit adjacent to the polar trophoectoderm.

Decidua capsularis: the layer that grows over the implanted embryo.

Decidua peritalis (parietal decidua): The rest of the decidua.
Parietal decidua: not in contact with the embryo but when the placenta grows the decidua capsularis contacts the opposite side of the uterus. The eventually become indistinguishable.
Only basilar decidua gets invaded by the cytotrophoblas.


What are the two fetal membranes?

Amnion - avascular, covers the fetus, the back of the placenta an up the umbilical chord. Bag that the baby is in. It faces the fetus.
Chorion - trophoblasts that surround the amnion. They were the trophoblasts that were in a sphere around the embryo in the blastocyst that become villi and then regress.

Together the amnion and chorion make up the amniotic sac.


How many vessels are in the cord and what is between them?

2 arteries and 1 vein. The vein carries oxygenated blood. Whartons jelly is between the vessels and is made of a network of myofibroblats surrounded by mucopolysaccharids. This keeps it distended and tough.

Fetal and maternal blood do not miss


What is hCG?

human chorionic gonadotophin. Two chain that shas alpha chain with FSH, TSH and LH.
The beta chains are all unique.
Produced by the trophectoderm cells of the blastocyst and then the syncytiotrophoblasts of the placenta.
Is detectable in the maternal blood/urine within days of implantation. Steep rise in the first few weeks then production slows down.


What are the functions of hCG?

hCG binds to the LH/hCG receptor and thus performs a similar to LH. Has a longer half life than LH.
It provides support to the corpeus leuteum and prevents it from regressing. The corpus leuteum doubles in size (thus regression if the corpus leuteum is stopped). It also stimulates the production of progesterone and estrogen by the ovary.

This enables the corpus leuteum to produce estrogen and progesterone, which prevent menstrutation and maintain the endometrium in a deciduated form. Progesterone also cause quiscence of the myometrium.

Can be used to predict the health of a pregnancy.

HCG levels are higher with multiple pregnancies and can also be indicative of a pathological pregnancy.


The fetal blood gas transfer. How does maternal and fetal blood differ?

Fetal blood is adapted to suck oxygen out of the mothers blood.
Fetal blood also has more haemoglobin and can carry more oxygen.

Bohr effect: As maternal blood picks up fetal matabolites the pH drops reducing the affinity for oxygen and increasing the dissociation of oxygen. The opposite happens on the fetal side.

Haldane effect: The capacity of haemoglobin to bind CO2 is related to the amount of bound oxygen. Thus, more oxygen is lost in the maternal blood the capacity for CO2 increases. The opposite happens on the fetal side.


What produces progesterone?

Initially produced by the corpus leuteum but then is produced by the syncytiotrophoblasts of the placenta at 6-10 weeks. It does this by converting LDL-cholesterol from the maternal blood into progesterone.

This means the ovaries can be removed after 6-8 weeks and this will not impact pregnancy because the corpus leuteum is not needed anymore. Surgery of the ovaries etc.


What are the functions of progesterone?

Maintaines uterine quiescence (myometrium) causing smooth muscle relaxation.
Produces the decidual reaction in the endometrium - laying down of glycogen in the stromal cells and morphological change.

Induces the formation of the decidua.


What are conditions of too much or too little amniotic fluid?

Not enough amniotic fluid (oligohydramnios) suggest a fetal kidney problem because of insufficient urine production.

Excess amniotic fluid (polyhydramnios) may indicate a swallowing defect (occurs sometimes in diabetic pregnancy).

500-1000 mls is swallowed per day. Also diffusion through early fetus skin and across fetal membranes to the maternal circulation.


How are estrogens produced for the fetus?

1000 fold increase in pregnancy. Made by the feto-placental unit. But the placenta lacks the 17 alpha hydroxylase which converts progesterones to androgens. So the placenta can not produce estrogen on its own.

Placenta produces progesterones - fetal circulation to the fetal adrenals and liver to create androgens which goes back to the placenta (syncytiotrophoblast) to produce estrogen.

85-95% of progestrone and estrogen are shuttled into the maternal blood.


When is preeclampsia more common?

During first pregnancies to a father. The mother is protected from prampsia if they have barrier free sex 12 months prior to conception (exposure to sperm). If there is a new partner that time is reset.


What are the cardiovascular changes during pregnancy?

Increased stroke volume and increased pulse rate. The peripheral vascular resistance is reduced to help with the increase CO (except in preeclampsia).

Occurs prior to 9 weeks of gestation. Therefore, not caused by progesterone or estrogen (level are too low at 9 weeks).

Increased blood volume by 50%. The haematocrit declines (diluted blood). Check values for pregnant woman when looking at blood tests. There is also cyclic change in blood volumes during menstruation. 500 ml lost in delivery and urinate the remainder away.

Probably not NO or Ang II but:
Uteroplacental unit produces lots of angiotensin II, which is a vasoconstrictor. Somehow the effect on the mother is blunted in normal pregnancy.

NO is produced by the endothelial cells. Causes arterial wall relaxation.


What are the adaptions during pregnancy for the immune system?

Change of the immune system to allow tolerance to the fetus but retain the ability to still fight infections. Some infections are less protected against as a result.

White cell count rises due to expansion of the neutrophils (not antigen specific). Lymphocyte cell counts do not change but changes to a CD4 Th2 response (less cell mediated killing).

The decidua conains no B cells, 10% of the leucocytes in the decidua are T cells and 70% of the leucocytes are NK-like cells. NK cells in the peripheral blood can kill by ADCC, but not uterine NK cells because they lack CD16.


What is the main cause of recurrent miscarriage?

Spontaneous miscarriage (not recurrent) is usually genetic abnormalities.

Women who have recurrent miscarriages have increased CD3 T cells in the decidua basalis. Immune attack on the embryo. Many dendritic cells also around.

Look at hCG levels and if they don't go up it is more likely to have a miscarriage.


What are the adaptions during pregnancy to the abdominal wall and skin?

Increased blood flow to the skin.
Warm clammy hands because flow to the hands increased 6-7 fold. Flow to the feet is increased. The baby is generation lots of heat so the blood flow to the skin is increased to loose that heat.

There are pigmentation changes in some area of skin nipples and areola.
Development of a linea nigra (line of pigmentation on tummy).
Chloasma may develop (discolouration of skin of the neck and face).
Pigmentation changes are due to increased secretion of melanocyte stimulating hormone.

Suntans develop well.

Women can get stretch marks (striae gravidarum): reddish slightly depressed streaks in of the abdomen, thighs and breasts.


What is the function of the decidua?

You don't need a decidua for pregnancy.

It is important for providing nutrients prior to tapping into the maternal blood supply.


What diseases are associated with the placenta?

Fetal origin of adult diseases - cardiovascular mortality higher in the mother later in life. Should be investigated.
Interuterine growth restriction
Fetal hypoxia/brain damage


What are the different types of villi?

Most villi do not come into contact with maternal tissues and are floating in maternal blood. These are called floating villi.

The villi initially surround the embryo in a sphere. The back and sides (chorion laevi) regress after exposure to maternal oxygen during the first trimester (around 7 weeks 5 days) and becomes the chorion. The villi at the base forms the definitive placenta (chorion frondosum)

Anchoring villi:
Cytotrophoblasts break through the syncytiotrophoblasts and cytotrophoblast columns invade deeply into the maternal uterus eating the glycogen from the fibroblasts. They anchor the placenta to the uterine wall. They also invade the spiral arteries and decidua during the first and second trimester.


What adaptions does the placenta have to increase transport across the placenta?

Tortuous with a large surface area.
Syncytiotrophoblast has a microvillous surface for increased surface area.
In the third trimester the fetal capillaries are closely apposed to the syncytiotrophoblasts.


What is the function of the amniotic fluid?

Buoyant medium that allows symmetric growth.
Cushions the embryo/fetus
Prevents adhesion of the fetus with the membranes
Allows the fetus to move to assist muscle development
Develop GI/ respiratory development - breathing and swallowing


Where does the amniotic fluid come from?

Initially it is ultra filtrate of maternal plasma
Major fetal contribution.
20+ weeks fetal urine

800 ml by term.


What are methods of diagnosis of fetal genetic diseases?

These are screens not diagnostic tests.

Chorionic villus sampling - biopsy of the placenta transvagina or transabdominal nd placenta villi are sucked out.

Amniocentesis - transabdominal injection to take a sample of the amniotic fluid - they contain amniocytes

Cell free DNA - blood test of the mother to detect free DNA from the syncytiotrophoblasts of the placenta.Use to identify trisomy 21.


What disease are and are not transferred across the placenta?

Are: HIV, CMV, small pox, rubella, tpoxoplasmosis

Are not: HepB, rabies, measles, malaria


What drugs can and can't cross the placenta?

Can: thalidomide
Betamethasone (glucocorticoid) can be given to the mother 3 days prior to premature delivery to cause respiratory development and prevent respiratory distress syndrome.
Recreational drugs
Paracetamol (safe)
Aspirin (safe)
Warfarin - crosses the placenta and causes fetal mutations
Heparin is safe.


What makes up a tertiary villus?

A tirtiary villi contains an outside layer of syncytiotrophoblasts, an under layer of cytotrophoblasts, villous mesenchyme and a fetal blood vessel.