Pregnancy Flashcards
Fertilisation means successful pregnancy
Trimester system is based on scientific model. T/F
What is a good indication that the pregnancy will last until term
No….. some estimations that only 1/3
F: only based on exprience and early understanding of pregnancy
a pregnancy completes the first trimester (13 weeks), it is very likely to last until close to the expected delivery time (term, 39-40 weeks).
What changes occur to mother, baby and placenta at which points
Maternal changes throughout
Embryo, foetus, viability (26 weeks), term
Placental changes- complex, mostly first half
What is absolute limit of infant survival
End of 2nd trimester 26-27 weeks
with modern medical science 23 weeks
Which things increase in a mother during pregnancy
Increased weight
Increased hormone levels / altered endocrine system
Increased blood clotting tendency
Increased basal body temperature
Increased breast size
Increased vaginal mucus production
Increased nausea and vomiting (‘morning sickness’)
…
….
What decreases during pregnancy and when
Blood pressure (2nd)
Why are pregnant women prone to collapsing
Decreased blood pressure
What other things are altered in pregnancy (not flat increase or decrease)
Altered brain function [1st & later]
Altered hormones [1st & later]
Altered appetite (quantity and quality) [1st & later] – GI imbalance
Altered fluid balance [2nd & later]
Altered emotional state [1st & later]
Altered joints [3rd]
Altered immune system [1st & later]
T/f implantation of the fertilised egg will occur around day 28
F! Fertilisation will occur within 24hrs of ovulation (day 14!) and implantaton would occur 3-5 days after fertilisation
Why can it be hard to identify when olvulaton occurred
he variability in length of the menstrual cycle was noted, making it difficult to identify (in a normal pregnancy) the exact timings of ovulation and fertilisation.
When is pregnancy counted
pregnancy is counted from the first day of the last menstrual period (LMP), with other events dated from this time. At least, this is the conventional timing from an obstetric-gynaecological view.
When would embryologist count emrbyo age from
An embryologist would start the count from fertilisation (wheter IVF or natural)… REFERRED TO AS PF (post-fertilisation)
What is the time difference between GA determined by LMP and the GA determined by conception
The GA determined by pregnancy will be 2-2.5 weeks longer than the embryo age
Because last menstruation would have occurred about 2 weeks (i.e. 14 days) before ovulation and fertilisation
Why does maternal weight change during pregnancy and when
on average will be in the range of 10-15 kg. This will include the weight of the fetus, amniotic fluid and placenta; increased fluid retention; increased nutritional stores (to feed the baby after delivery).
2nd and especially 3rd trimester
Why does blood clotting tendency increase and when
Why is blood clotting change in pregnancy and anomaly
From 2nd trimester
To reduce bleeding in delivery?
Anomaly because We are very used to the concept that increased blood clotting and increased blood pressure are parallel changes, as it is well established that hypertension is strongly linked to an increase in stroke and heart attacks.
In pregnancy BP decreases though
When does blood pressure decrease and why.
Impact
Maternal blood pressure is lowest during the second trimester,
and increases the risk of maternal fainting – so pregnant women should not stand for prolonged periods of time
What happens to BP during the 3rd trimester
Blood pressure tends to increase during the third trimester, but should still remain below a level that would be considered as hypertension; 120/70 mmHg would be considered normal.
What happens to basal body temp in pregnancy and why
Basal body temperature increases by ~0.5°C in the second half of the menstrual cycle after ovulation and is sustained into the first trimester of pregnancy, probably by the thermogenic roles of progesterone.
As the fetus increases in size, it contributes to maternal temperature, and normal maternal temperatures may exceed 38°C.
What happens to breast size in pregnancy and why
From first trimster
Breast size increases
dependent on increased hormone levels in the maternal circulation (human placental lactogen, prolactin, and ostrogens are all involved)
Why can women get increased clear discahrge in pregnancy
increased vaginal mucus production
is common and normal change in pregnancy
What is hyperemesis gravidarum
The most servere version of morning sickness (affects 1-2% of pregnancies whilst morning sickness generally affects 80%)
T/F morning sickness involves sickness specifically in themorning during pregnancies
F: ‘Morning sickness’ is not really an accurate name, as nausea and vomiting can occur at any time of day!
How does brain function change in pregnancy
The high levels of steroids, particularly progesterone, are thought to influence brain function during pregnancy, but due to the difficulties of doing detailed studies during pregnancy a precise understanding is lacking
Brain size actually decreases a bit! (might not have functional significance)
What happens to appetite during pregnancy
As the size of the uterus increases during the later stages of pregnancy, it imposes steadily increasing pressures on the gastro-intestinal system, including the stomach. This can decrease the distensibility of the stomach, and in late pregnancy the mother may need to have up to 6 smaller meals per day, rather than 3 bigger meals.
What happens to fluid balance in pregnancy
Kidney function changes in the mother as pregnancy proceeds leading to increased fluid retention and a higher plasma volume. BLOOD VOLUME IS 50% HIGHER THAN BEFORE PREGNANCY!
What happens to urination frequency in pregnancy
1st tri. increases (thought to be due to changes in the maternal hormones, regulating altered kidney function)
2nd tri. normalises
3rd increases (greatly enlarged uterus will be exerting pressure on the bladder)
During the 3rd trimester, the mother will be passing more urine in each visit to the toilet. T/f
F: By the third trimester, the greatly enlarged uterus will be exerting pressure on the bladder, decreasing the maximum size and volume of urine it can contain, so the mother will pass smaller volumes of urine more frequently.
What happens to emotional state during pregnancy
due to changes in hormone levels
motional changes linked to pregnancy can be very variable.
In some cases women are said to ‘glow’ with their pregnancy and with happiness – they are delighted to be pregnant, and the world is wonderful.
Alternatively, women may be equally happy to be pregnant, but may be emotionally very labile, crying with little or no obvious cause; or they may become clinically depressed during pregnancy, which may continue into post-natal depression.
Why do altered joints occur in pregnancy
Changes to the maternal pelvis, making the connections between the bones more flexible are necessary to permit the delivery of a normally-grown human infant.
Condequence of joint changes to materna pelvis for flexibility in pregnancy
Parallel changes are observed in other maternal joints, and these generally persist after pregnancy, causing permanent modifications to joint structure and (modestly) function.
How do changes in immune system occur in pregnancy
Baby is non-self but there is no immune response against it:
- Suppression of maternal immune system at utero-placental interface. Cooperate to reduce Th1 and increase Th2
- HLA antignes on placenta in contact with maternal tissue. Usually HLA very polymorphic, but these placental HLA are almost invariant.
HLA G (placental) has just 5 sequence variants.. HLA G could provide an immunological signal that shows that the tissue is human. Suppresses leuocyte activity too
When does hCG peak
8 weeks
this could be involved in morning sickness, which also increases at 8 weeks
When do the placental hormones peak and why, what are they
Placental lactogen
Oestrogen
Progesterone
All increase up to a peak in the 3rd trimester (parallel increasing size of the placenta)
What is hCG produced by
Also the placenta, but its regulation is different other placental hormone groups, which all peak much later (in third trimester, not third like hCG) in line with placental size
Why is there small increase in the progesterone and oestrogen at the beginning of the GA
Fertilisation occurs after day 14 of mensutraul cycle
Then the menstrual cycle continues for 2 weeks, so this represents the luteal phase of the menstrual cycle
You can compare the difference between menstrual cycle hormone concentration and concentration in pregancy
What is the main oestrogen in birth
Oestriol
Why is progesterne imprtnat in pregnancy
The very high levels of progesterone are of particular importance, as progesterone is the key hormone in allowing the pregnancy to continue. Low progesterone levels, or administration of a progesterone antagonist, will lead to loss of the pregnancy at all gestational ages.
What happens to gonadotrophns during prengancy
The maternal endocrine system is modified substantially during pregnancy, with the high levels of steroids suppressing the HPG, leading to very low levels of LH and FSH throughout pregnancy, and hence no cyclic ovarian or uterine functions.
What is the source of progeserone during early pregnancy
From the time of fertilisation to about 8 weeks gestation, the corpus luteum is the main source of progesterone, and this production is sustained by the rapidly increasing levels of hCG
T/F the placenta does not produce progesterone in the early part of pregnancy
F… The placenta can also produce progesterone as well as corpus luteum, but in the earliest weeks of pregnancy, the small size of the placenta means that its net contribution to maternal progesterone levels is limited.
What is the source of progesterone after the early pregancy
Increasing placental size means that it contributes increasingly to the levels of progesterone after 8 weeks in the maternal circulation, and by 10 weeks of gestation the placenta is the source of all progesterone.
T/f the corpus luteum still produces progesterone after week 10 but main progeserone production is from the placenta
F:
From about 6 weeks of gestational age, the corpus luteum gradually produces less progesterone (despite the very high hCG levels), and by about 9 weeks it has ceased to make steroids
What is the luto-placental shift
Change in progesterone production from corpus luteum to placenta at 8/9 weeks
Where is oestrogen produced early and later in pregnancy
Early weeks corpus luteum (mainly 17b-oestradiol)
After luteo-placental shift, oestrogens produced involving complex interaction between placenta and foetal adrenal glands
Outline oestrogen production in the placenta and foetal androgen gland
I. 17b-oestradiol
II. Oestriol
Placenta doesn’t contain enzyme needed for androgen production from pregnenolone (we need to produce androgen before oestrogen)
17b-esotradiol:
So pregnenolone from placenta is converted to a weak androgen, DHEA, in the foetal adrenals using 16aOH.
But we don’t want the DHEA to have androgenic effects, as the foetus might be a girl, so we sulfate the DHEA DHEA-S (also in the adrenals)
DHEA-S is then taken back to placenta, where it is converted to 17b-oestradiol.
Oestriol:
pregnenolone again converted to DHEA in foetus, and sulfated to DHEA-S.
DHEA-S is taken to the foetus liver, where it converts DHEA-S to 16aOH-DHEA-S.
This is then taken back to the placenta where it is converted to estriol
What enzyme is required for conversion from pregnenolone to andrgen
Cytochrome P450 17,20-lyase
What are the precursors for 17b oestradiol and estriol in the placenta (produced using the baby’s adrenals)
DHEA-S for 17b oestradiol
16aOH-DHEAS-S for oestriol
What is development of strucutre in utero depend on
Genetic control + interaction with environment incl maternal nutrition
What is evidence of genetic basis of contorl of development of structures
Chromosomal abnormalities provide the clearest evidence of such genetic regulation. All cases of too many chromosomes or too few chromosomes show changes in development.
What is the only viable example of too few examples
he only viable example of too few chromosomes is Turner’s Syndrome: 45 chromosomes, with one X-chromosome (45 X0). Loss of any autosome (chromosomes 1-22) leads to non-viability, as does 45 Y0).
Examples of loss of autosomal chromosomes
None, this is non-viable
Examples of extra set of sex chromosome adn of extra autosom
Extra sex chromosomes (XXX, XYY, XXY (Kleinfelter’s syndrome)) have modest effects, and the only viable autosome trisomy is Down’s syndrome (chromosome 21 trisomy).
When is embryo most vulnerable to teratogens
Early development of the human embryo is vulnerable to teratogens
(mostly up to 7 weeks embryo age)
Define teratogens
factors that can affect the details of development, although the primary structures will be present
Which organ systems develop late in pregnancy (last few weeks)
and why
he lungs, the digestive system, the immune system and the brain.
fetus has limited need of them in utero, whereas they become much more important after birth, so their late development is logical.
However, this means that in a preterm infant, they may not function correctly, and thereby cause illness or death to the infant.
In addition to being affected by teratogens, what other problems occur in early stage of development
Other complications of human development, including spina bifida and cleft palate, also occur in this early stage of development.
Define conceptus
everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)
Define embryo
the baby before it is clearly human
Define fetus
the baby for the rest of pregnancy
Defie infant
– less precise, normally applied after delivery
Why the difference between fertilisation and implantation
Fertilisation usually occurs in ampulla
Takes a while to get round the fallopian tube and be implanted ino the lining of the uterus
What occurs between fertilisation and implantation
The cells of the embryo are undergoing mitotic (cleavage) division, deriving their nutrients from the secretions of the Fallopian tube.
Distinguish the two meanings of embryo
During week 1 PF, refers to while conceptus
After differentiation to form a blastocyst, the embryo refers to the cells that contribute to (or are) the baby alone; other tissues have separate identities.
T/f most of the second half of pregnancy is concerned with forming the strucutres
F
Once the main structures of the baby have formed (Figure 3.6) during the first months of pregnancy, the rest of pregnancy is more concerned with growth of the fetus, and the maturation of the structures that have been developed
Approximate weight of baby at end of 1st, 2nd and 3rd trimester. What does this sho
1: 50g
2: 1050g
3: 2100g
Shows most of the growth occurs in 2nd and 3rd trimester and structure formation in the 1st
t/f structures required high levels of oxygen to form
F…. formation of structures in trimester 1 takes place in low oxygen environent (3%)
Key events in 2nd week of development
Development of bilaminar dsic
Key events in 3rd week of development
Formation of trilaminar disc (mesoderm), CNS &; somites.
Blood vessel initiation. Formation of placental villi. (3mm).
Key events in 4th week of development
Closure of neural tube. Heart, Face, arm initiated.
Umbilical cord. Elaboration of placental villi. (4mm)
Key events in 5th week of development
Face & limbs continue. (5-8mm)
Key events in 6th week of development
Face, ears, hands, feet, liver, bladder, gut, pancreas. (10-14mm)
Key events in 7th week of development
Face, ears, fingers, toes
Key events in 8th week of developement
Lungs, liver, kidneys, (28-30mm)
What is the bilaminar disc
In the blastocyst , there is a circle of trophoblasts with a bilaminar disk of epiplasts and hypoplasts across the centre
Function of the placenta
Separation Exchange Biosynthesis Immunoregulation Connection
Outline the ‘connection’ function of placenta
The placenta must make sufficiently strong connections with the underlying maternal decidua to last for the 9 months of pregnancy.
How do we know that the placenta is the key tissue in immunoregulation
Even when there is implantation other than in the uterus, there are still some survivals (ectopic) showing it is not the uterus responsible for preventing an immune attack of the fetus
Primary subunit of the placenta
Villus
What allows exchange between maternal adn fetal vascular system
Villus, which has the complex branched structure shown. This provides a very large surface area (estimated to be 11 square metres) for exchange between the maternal and fetal vascular systems, thus meeting a primary requirement for exchange
What can be found in villi
ithin each villus there is a complex blood supply, including arterial and venous vessels, connected to smaller capillaries in the terminal portions of each villus.
What is the oxygen content of veins and arteries for foetal musculature to and from the placenta
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 fetus during pregnancy
(i.e. travelling away from the baby heart to the placenta is artery, travelling from the placenta to the heart is vein)
What is the maternal surface of the placenta subdivided into
How many villi in each
cotyledons (30-60 per placenta)
each cotyledon contains one or more villi, with larger cotyledons containing more villi.
Outline the strucutre of the conceptus once it has implanted within teh maternal decidualising endometrium
At day
There is epiblast and hypoblast. Amniotic cavity within the epiplast layer
Then exoxoelomic cavity (primative yolk sac)
This is surrounded by cytotrophoblast
Which is surroundd by syncitiotrphoblast
In which cell layer of the conceptus does the placenta develop
From the cytotrophoblast
What is special about syncytiotrophoblasts
This outerlayer is multinucleated cells and containing fluid-filled lacunae
How does placenta develop
After implantation.
Cytotrophoblast proliferate into the syncytium (with the lacunae)
Forms a cytotrophoblast column). Which then undergoes branching (villus sprouts)
At centre of each villus is a mesenchymal cell (=extra-embryonic mesoderm), from which villus vascular system develops.
Note that the lacunae in the syncytium become intervillous spaces!
SO NOTE THAT THE VILLUS IS MADE FROM THE CRTOTROPHOBLAST, WHILST THE VASCULAR SYSTEM IN THE VILLUS IS MADE FROM EXTRA-EMBYRONIC MESODERM
How does the structrue of the villus change through pregnancy
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.
Why are there fewer crytotrophoblasts present near term
This will maximise the efficacy of nutrient transfer into the fetal blood, and enhance fetal growth in later pregnancy.
T/F the conceptus never makes contact with the maternal capillaries
F…. As it grows, it makes transient contact with the maternal capillaries before it is isolated from maternal capillaries
How is the conceptus separated from the maternal blood
the rapidly proliferating cytotrophoblast cells form a shell around the conceptus (Figure 3.16), isolating it from maternal blood by about 4 weeks post fertilisation.
Note that the placenta then forms by branching of these cells into the synctytium
What provides nutrition for the developing embryo
1st trimester:
DECIDUAL GLANDS of the uterus hypertrophy to provide nutrients for placenta and baby= histotrophic nutrition
LATER:
Maternal blood=haemotrophic utrition
What is the cytotrophoblast shell
From the cryptotrophocyte layer. Blocks spiral arteries, preventing maternal blood from filling the intervillous space until 10 weeks GA (8 weeks PF)
When does the cytotrophoblast break down and why
During weeks 10-12 (GA), the cytotrophoblast plugs gradually break down, beginning with those at the periphery of the placenta, and ending with those near the centre.
Note that the development of structures mostly occurs in an anaerobic environment
spiral arteries providing maternal blood to the placenta, and hence forming the main supply of nutrients to the developing placenta and fetus.
Name a particularly risky time in pregnancy
When the cytotrophoblast plug breaks down, maternal blood enters the intervilous space.
if the placenta is not fully anchored to maternal decidua, the increase in pressure as it is exposed to the maternal arterial supply can detach the placenta and lead to miscarriage (late first trimester)
SUMMARY OF NUTRITION AND PLACENTA DEVELOPMENT
So conceptus has some contact with maternal blood during growth, but soon isolates itself with the cytotrophblast layer.
The cytotrophoblasts branch into the syncytium to form columnar structures which become branching villi.
Cytotrophoblast cells also block spiral arteries of the mother until about week 10 GA
Up until this point, maternal blood is not the source of nutrients, instead there is hypertrophy of deciduous glands in the endometrium which supply nutrients to placenta and baby
Then, at 10-12 GA, the Cytotrophoblast plug is broken down and maternal blood flows in the intervillous space , becoming the source of nutrient for the baby
How to cytotrophoblasts affect spiral arteries
- Block them until week 10 GA
2. Remodelling
How do cytotrophoblasts remodel spiral arteries
the vascular endothelium, and underlying smooth muscle cells are lost, and replaced by cytotrophoblast. This remodelling process begins during the first trimester, and continues until weeks 16-18 of gestation.
What is the point of the cytotrophoblasts remodelling spiral arteries
critical for later growth of the fetus, as it converts the narrow, vasoactive spiral arteries to wide-bore vessels that can transport very large volumes of maternal blood to the placenta, and hence provide the quantities of nutrients needed. The lack of smooth muscle cells in these remodelled vessels is important, as this means that the blood flow remains high as these arteries cannot respond to vasoconstrictors.
Why can no pain be felt during the cutting of the umbilical cod
The placenta has no nervous system, so it is not regulated by such systems at any stage of pregnancy. This means that it can feel no pain during delivery, and the umbilical cord can be cut after delivery without any impact on the infant.
What is the main methofd of regulation of placental growth and dvelopment
In general terms, the placenta regulates its own growth and development through autocrine mechanisms.
It produces a rnage of GFs and proteins
The maternal decidua mainly seems to modulate (restrain) placental growth and development, so that the placenta is optimal for both the mother and the fetus
T/f normal human pregnancy poses great risk to mother
F. It is the process of labour and delivery that poses the dominant risk and is the commonest cause of maternal death linked to pregnancy
Why are mothers should to blood loss after delivery? What limtits this
The remodelling of the uterine spiral arteries (see Session 3.3) means that these vessels can lose relatively large volumes of blood after delivery.
his should be limited by contraction of the uterus after the placenta has been delivered, which diminishes the blood loss very strongly. Sometimes it is necessary for drugs to be given to ensure this happens correctly.
Why is it important that all of the placenta is delivered
Placental tissue is relatively inflexible, and any left within the uterus will prevent the contraction of uterine tissue, and permit continued blood flow through the spiral arteries into the uterine lumen.
What poses biggest risk to infant during pregnancy
defects in the production of gametes, so that they contain too few or too many chromosomes. Loss of any autosome is not compatible with life
Changes in sex chromosomes are generally less severe
Which of these are viable genotypes:
43XX 43 XY 44XXX 44XXY 44XYY 44XO 44YO
43XX=no 43 XY=no 44XXX=yes 44XXY= yes 44XYY=yes 44XO =yes (but more severe than gain of sex chromosome= turner's, infertility) 44YO=no
When are placental problems most common. What are the common placental problems
In first trimester
Some will be due to developmental problems affecting the embryo/fetus or placenta, others will result from detachment of the placenta in late first trimester
What is key problem for pregnancy after the limits of viability (23 weeks GA) have been passed?
early delivery of the infant
Why are infants delivered early
- Labour starts befroe term
2. Deteriorating maternal or foetal health (delivery is best option to save life of mother or child)
What is stillbirth
death of an infant within the uterus, so that it is delivered without any signs of life.
Sometimes,
deliveries before viability are miscarriages, and after are stillbirths
Why can stillbirth happens
Pregnancy complication, or labour complication
T/f stillbirth only occurs pre-term
F: stillbirth can occur at any gestational age, including term;
Reason for higher stillbirth rate in developing coutnries
availability of monitoring equipment, coupled with access to facilities for an emergency Cesarean section if complications in the infant are detected
Give examples of why infants are delivered early to save life of baby, mother or oth
Growth Restricted infants, and Pre-eclamptic pregnancies
Why are babies born before 32 weeks GA at risk
incomplete development of their lungs, digestive system, brain and immune system
At which GA are you at severe risk of complications due to preterm delivery
Before 32 weeks GA= very preterm (lung, digestive, brain and immune problems)
Moderately preterm= 32-37 weeks of gestation….. much less risk
Why can we not definitively only classify ‘viable’ babies as stillborns, and non-viable as miscarriage
Given that the viability of an infant born at less than 28 weeks gestational age is so variable, it is hard to provide a completely rigorous time definition, so ‘delivered without any signs of life’ may be the best option.
Rate of stillbirth in UK
0.35%, or 2,600 infants per year, so a large hospital with 4,000 deliveries per year is likely to have 10-15 cases per year.
What could indicate increased risk of stillbirth
The detection of stillbirth depends on monitoring of fetal wellbeing; a decrease in, or lack of, fetal movements may indicate an increased risk
What is preferred method for checking for stillbirth
The preferred method is ultrasound assessment of the infant, perhaps coupled with assessment of the fetal blood flow (doppler ultrasound)
Causes of stillbirth
not well understood; about 50% of cases are thought to occur during the process of labour, which emphasises the importance of monitoring fetal wellbeing during pregnancy
Is risk of stillbirth increased in subsequent pregnancy
Some studies have suggested that the risk of stillbirth is increased in a subsequent pregnancy, but it is not clear if this is universally applicable, or what the mechanism might be.
Outline the 4 things which the conceptus refers to
The embryo, the placenta, the foetal membranes and the umbilical cord
