Pregnancy/Labour Flashcards
How can human pregnancy be divided into?
3 Trimesters - defined by experience
1st trimester: 0-13 weeks - If the pregnancy gets to the end of the 1st trimester it is very likely to continue successfully.
2nd trimester: 14-26 weeks - Without a neonatal intensive care they are highly unlikely to survive.
3rd trimester: 27-40 weeks
There are maternal changes throughout the 3 trimesters - 1st trimester difficult to see they’re pregnant. 2nd and 3rd you can see they are pregnant. The placental changes are complex
See diagram
Describe the maternal changes in pregnancy and in what trimesters?
Increased weight [3rd]
Increased blood volume [2nd & later]
Increased blood clotting tendency [2nd & later]
Decreased blood pressure [2nd] - Postural hypotension, fainting
Altered brain function [1st & later]
Altered hormones [1st & later]
Altered appetite (quantity and quality) [1st & later] – GI imbalance, Hyperemesis gravidarum (morning sickness)
Altered fluid balance [2nd & later]
Altered emotional state [1st & later] - postnatal depression
Altered joints [3rd] - joints become more flexible
Altered immune system [1st & later] - the foetus and placenta are rejected as foreign bodies
Describe maternal changes in the endocrine system
HCG - reaches the peak around 8 weeks during gestation in the 1st trimester. Correlated to morning sickness.
Progesterone oestrogens and placental lactogen all increase gradually. This increase is due to the gradually increase in the size of the placenta. Progesterone>Oestrogens>Placental lactogen
These hormones fall when the placenta is delivered. Progesterone is required to maintain pregnancy - this is important.
All of these hormones are produced in the placenta
Summarise the risks pregnancy has on the mother?
Relatively little risk in the early parts of pregnancy, the main risk to maternal health (or life) linked to delivery
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. It is about 8 weeks when you start describing the embryo as a fetus.
Define infant
less precise, normally applied after delivery
Describe the development from blastocyst to fetus
1) Blastocyts - 9 days. consists of bilayer of epiblast and hypoblast cells. Starts off as a ball of cells.
2) Embryo - 5-6 weeks.
3) Fetus - 3 months.
The timings refer to post fertilisation. Counting from when fertilisation happens.
When do you start counting pregnancy. How is pregnancy is normally counted.
1st day of the last menstrual period - this system is used because it is easier for the women to remember when their last period was. Embryology timings are different!
How can you observe human pregnancy?
Measurements can be made of circulating factors or dimensions
Scans
What determines pregnancy lengths between different species?
Essentially the length of pregnancy correlates to how big the baby is when its born
What are teratogens?
An agent or factor which causes malformation of an embryo. Exposure of the embryo to teratogens early on can cause problems. The first 8 weeks of development is when the embryo is most vulnerable. See slide
Describe the placenta on the fetal side
20 cm wide
Umbilical cord attached in the middle
Around the placenta are membranes - fetal-placental membranes which surround the baby and hold the amniotic fluid in place during pregnancy.
Describe the placenta on the maternal side
Placenta is made up of sections of tissue called cotyledons - usually small at the edge and bigger in the middle. These are the functional subunits of a placenta.
Describe the basic placental structure
See slide
Placental vilus:
Very highly branched structure, provides a large surface area (~11m2).
Very effective for transport of molecules between maternal and fetal circulations.
Also anchors the placenta (and hence the baby) securely for 9 months.
Intimate contact between maternal and placenta tissues – cytotrophoblast layer separates the main maternal blood supply from the placenta itself. This anchoring of the placenta must take place properly - if this cytotrophoblast layer breaks down then the high blood pressure of the mother may go in and move the placenta causing a miscarriage in the 1st trimester.
Cytotrophoblast shell limits blood (oxygen) supply to embryo during early development. The embryo requires a low oxygen environment for it to develop - oxygen holds a potential to generate free radicals.
Remodelling of spiral arteries allows high volume blood supply in trimesters 2 and 3, when infant growth is greatest. It remodels so the it is no longer vascular smooth muscle which can contract.
What are the placental (or villous) functions?
Separation - separates blood supply Exchange Biosynthesis Immunoregulation - means the mother immunesystem doesn't reject the conceptus. Connection
Describe placental development
Starts as a layer of single cells in the blastocyst (see slide 11)
These proliferate and differentiate
Form simple branched structure, expands iteratively. Chorionic villus grows and develops until it starts to fold back on itself
See diagrams
What happens when you get placental mal-development
Miscarriage (late first trimester)
Miscarriage (second trimester)
Pre-eclampsia (early delivery)
Fetal growth restriction (small infant)
Define miscarriage
loss of a nonviable pregnancy (<23 weeks of gestation)
Define term
This is a time frame of 37-42 weeks when the baby is ready for extra uterine life.
Define preterm
Is any baby delivered before 37 weeks of gestation
23-37 weeks of gestation
We can initiate early labour when the baby is in danger or if the mother is danger. E.g the mother has pre-eclampsia - high blood pressure.
Define labour
Uterus is undergoing regular coordinated contraction.
The fundus is where the contractions start and go down pushing the baby towards the cervix.
Cervical ripening and effacement
Describe the process of labour
Independent of gestational age:
1) Cervical ripening and effacement (increasing)
2) Co-ordinated myometrial contractions (increasing)
3) Rupture of fetal membranes - keeps the amniotic fluid in.
4) Delivery of infant
5) Delivery of placenta
6) Contraction of uterus
Describe the labour stages
See diagram Latent stage (~8 weeks) - where you get braxton hicks contractions = partial contraction of the uterus. "Uterus training"
Labour can last up to 48 hours:
Phase 1 - contractions increase in force, cervical changes. This phase take many hours
Phase 2 - baby delivered
Phase 3 - delivery placenta
What causes the initiation of labour?
Term - normal labour
- Not really sure!!!
- Estrogens; low progesterone?; CRH?; oxytocin?
Preterm - early labour - Intrauterine infection - Intrauterine bleeding - Multiple pregnancy - Stress (maternal) - Others Inflammatory changes are strongly linked with labour Activators of inflammation are readily linked with preterm labour (eg intrauterine infection)
Describe cervical ripening and effacement
Change from rigid to flexible structure
Remodelling (loss) of extracellular matrix
Recruitment of leukocytes (neutrophils)
Inflammatory process
- Prostaglandin E2, interleukin-8
- Local (paracrine) change in IL-8
Describe coordinated myometrial contractions
Fundal dominance
Increased co-ordination of contractions
Increased power of contractions
Key mediators
- Prostaglandin F2a (E2) levels increased from fetal membranes
- Oxytocin receptor increased
- Contraction associated proteins
Describe the rupture of fetal membranes
Loss of strength due to changes in amnion basement component
Inflammatory changes, leukocyte recruitment
- Modest in normal labour, exacerbated in preterm labour
Increased levels and activity of MMPs
Inflammatory process in fetal membranes
Summarise the tissues and process in labour
Cervix
- Prostaglandin E2, interleukin-8, MMPs
Myometrium
- Prostaglandin F2a (E2) levels increased from fetal membranes
- Oxytocin receptor increased
- Contraction associated proteins
Fetal membranes
- Inflammatory process in fetal membranes
- PGs, interleukins, MMPs
What is NF-kappaB?
Pro-inflammatory transcription factor - NF-kappaB upregulates inflammatory factors such as COX-2, IL8, TNF-a, oxytocin receptor, IL-1beta(this interleukin has a positive drive on NF-kappaB) etc
Many different initiators can activate NK-kappaB and drive all the process of labour.
Almost all pro-labour genes have NFkB binding domains in their promoters
Modification of NFkB sites in promoter sequences leads to loss of expression in cells or in expression vectors
Describe the control of term labour
CRH and PAF are important in controlling labour.
CRH levels increase very sharply in the 3 weeks before delivery in human pregnancy.
PAF: Platelet activating factor Part of lung surfactant Surfactant proteins and complexes Produced by maturing lung, before birth Levels in amniotic fluid increase near term Fetal signal of maturity
CRH and PAF stimulate prostaglandins E2 and COX2.
CRH and PAF can upregulate inflammatory pathways in fetal membranes. Initiators of term human labour.
1) Lungs mature - produce PAF which upregulates inflammatory process in the fetal membranes
2) Plancenta is the source of the CRH - increases CRH which also upregulates inflammatory processes. It goes into the baby which stimulates the anterior pituitary to release ACTH which stimulates the adrenal glands to produce cortisol. Cortisol activates lung maturing and also goes back into the placenta via the umbilical cord and stimulate more CRH production.
- Anything that increases CRH may predispose to labour (stress, multiple infants)
- Anything that increases muscle contraction may predispose to labour (excess stretch of uterus)
- Anything that activates inflammatory cascades may predispose to labour
- The above apply to preterm labour (intrauterine infection, bleeding, twins)
Describe the effects of progesterone in human pregnancy
Progesterone is NEEDED to sustain pregnancy
- Progesterone receptor blockade: pregnancy loss
Progesterone levels remain very high until after delivery of the placenta (unlike sheep)
Effect of progesterone lost in normal term labour
PR-B mediates the main effects of progesterone via gene expression
PR-A is less able to mediate these effects
Ratio of PR-A : PR-B increases at term
Loss or change in PR may lead to ‘functional progesterone withdrawal’
