Labour Flashcards
What is defined as miscarriage?
<23 weeks gestation
Term vs. Pre-term?
Term - 37-41 weeks
Pre-term - 23-47 weeks
Define Labour
Increasing FUNDALLY-DOMINATED CONTRACTIONS combined w. increasing cervical ripening and effacement
What does the process of labour involve?
Labour involves: • Cervical ripening and effacement – INCREASING • Co-ordinated myometrial contractions – INCREASING • Rupture of foetal membranes • Delivery of infant --> then delivery of placenta • Contraction of uterus
Explain the stages (terms) of labour
Involves:
• 3 trimesters
3rd trimester made up of 3 phases:
• Phase 1 - many hours
• Phase 2 - hours (baby delivered)
• Phase 3 - 30mins (placenta delivered)
What is thought to initiate labour both during ‘term’ & ‘pre-term’?
Term:
• NOT SURE
• may be oestrogen, LOW progesterone, CRH OR OXTC
Pre-term: • Intrauterine infection • Bleeding • Multiple pregnancy • Stress (maternal)
State the 3-stage part of the labour process
(1) Cervical ripening & effacement
(2) Co-ordinated myometrial contractions
(3) Rupture of foetal membranes
Explain (1) of the labour process
(1) Cervical ripening & effacement
- change from rigid –> flexible structure
- remodelling (loss of ECM)
- recruitment (of leucocytes e.g. neutrophils)
- inflammation (PGE2, IL-8)
Explain (2) of the labour process
(2) Co-ordinated myometrial contractions
- A FUNDAL dominance (w. increased power & co-ordination of contractions)
- Key mediators (PGE2, OXTC receptors increase, contraction proteins)
Explain (3) of the labour process
(3) Rupture of fetal membranes
- Loss of strength due to changes in amnion BM component
- Inflammation & leucocyte recruitment (exacerbated in preterm labour)
- Increased MMPs
Summary of tissues and processes in the cervix, myometrium & fetal membrane?
o Cervix
• PGE2
• IL-8
• MMPs
o Myometrium
• PGE2 F2alpha increased from fetal membranes
• OXTC receptor increased
• Contraction associated proteins
o Fetal membranes
• Inflammatory process in fetal membranes
• PGs, ILs, MMPs
Explain NF-kB
Pro-inflammatory transcription molecule
Has MANY initiators so can induce MANY effects (mainly inflammation) through:
• COX-2, IL-8, IL-1B, MMPs, OXTC/PG receptors, contraction associated proteins
Evidence to support that NF-kB has many initators?
Pro-labour genes have NF-kB binding domains in promotor regions
Modification of NF-kB sites in the domains led to loss of expression of the cells
What is a key regulator of labour?
NF-kB
What is strongly linked with term labour?
Constitutive PGE2 synthesis
• expressed BEFORE any changes can be witnessed
Equally, some tissues could NOT be stimulated to express PGE2 as the levels are ALREADY HIGH
Where does control of labour mainly come from?
CRH & PAF
These then activate other molecules and ultimately MMPs, PGE2 & upregulation of OXTC receptors
(onenote image!)
What do CRH & PAF stand for?
CRH - corticotrophin releasing hormone
PAF - platelet activating factor
Explain the link between CRH & labour
Produced not only by PG BUT also by the HUMAN PLACENTA
- Levels RISE @ end of pregnancy
- CRH-binding proteins DROP towards end of pregnancy
High CRH correlated w. HIGH COX2 expression
Explain link between PAF & labour
Part of lung surfactant that is produced by maturing lungs BEFORE birth
• levels in amniotic fluid INCREASE near term (as PAF part of surfactant that also increases)
HENCE levels of PAF are a signal of foetal maturity (may stimulate labour)
What can BOTH CRH & PAF upregulate?
Expression of PGE2 & COX2
IL-1beta (inflammatory mediator) levels
[cannot prove however as unethical!)
What is the hypothesis of parturition?
PAF
• directly made by the lungs
• acts to create ILs which stimulates PG production
CRH
• made primarily by placenta
• stimulates the baby hypothalamus & adrenals to produce cortisol
What is odd about the cortisol production in the placenta?
Cortisol has a +VE feedback of CRH production in the placenta
What are potential theories drawn for labour from the parturition hypothesis?
- Anything that INCREASES CRH may = labour
• e.g. stress, multiple infants - Anything that INCREASES MUSCLE CONTRACTION may = labour
• e.g. xs stretch of uterus - Anything that ACTIVATES INFLAMMATORY CASCADE = labour
ALL the above also applies to pre-term labour
• i.e. stress due to intrauterine bleeding etc.
Why is Progesterone needed in pregnancy?
To SUSTAIN pregnancy
i.e. if P.Receptor-blockade = pregnancy loss
What has been found about Progesterone levels during pregnancy?
Levels remain VERY HIGH
• UNTIL the delivery of the placenta
i.e. the effect of Progesterone LOST in normal term labour
Explain the interaction between NF-kB and Progesterone
HIGH LEVELS of NF-kB BEFORE TERM
• can BLOCK the PRs
• hence REDUCE the effect of P. to sustain pregnancy
• SO can begin labour
i.e. NF-kB levels are HIGH towards end of term so….!
Explain the 2 kinds of PR
PR-B
• mediates main effects of P.
PR-A
• less able to mediate than PR-B
Ratio of PR-A:PR-B INCREASES towards TERM so P. has LESS of an effect
What can loss or change in PR lead to/
A ‘functional P. withdrawal’ which is physiologically normal towards term labour
What effect does P. has on labour pathways?
Can SWITCH OFF MANY labour pathways
onenote picture!!
What does labour strongly resemble & the main active tissues?
Labour strongly resembles an inflammatory response in
• fetal membranes & cervix
Main active tissues are
• myometrium & cervix