Labour Flashcards
Define labour
Regular painful contractions associated
with cervical change (± spontaneous
rupture of fetal membranes)
* End result is delivery i.e. expulsion of
the fetus(es), placenta and membranes)
– also called “parturition”
Changes in the cervix in 3 stages define labour process:
1. first stage = onset of full cervical dilation (10 cm)
- before labour cervix is thin and long (10 cm) but during this stage cervix dilates and gets shorter.
2. second stage includes full dilation to delivery of the fetus.
3. Third stage includes delivery of fetus to delivery of placenta.
What is the major transition for successful labour?
myometrium = quiescent to contrtile
cervix = closed to open
membrane = intact to rupture
=> the hormonal changes don’t only induce contractility some hormones / factors such as relaxin and collagenase and elastase induce dilation
=> We want contraction in the myometrium and dilation in the cervix in labour for successful labour
What’s different about myometrium( uterus muscle) compared to other body muscles?
Other muscles contract and relax whereas myometrium constantly contracts during labour
What factors are involved in quiescence phase of labour?
-Progesterone, PGI2, Relaxin
-Parathyroid hormone -related peptide (PTHrP
-Calcitonin gene -related peptide, vasoactive intestinal peptide
-nitric oxide (NO)
=>all these lead to increased intravenously (cAMP/cGMP) which inhibits the release of intracellular calcium for myometrial contractility seen in labour
What regulates activation phase?
Rise in oestrogen
Mechanical stretch
Up regulation of panel of genes required for contractions: prostaglandin and oxytocin receptors (OTRs) all contribute to activation phase.
As labour progresses….
- uterus made of vertical and horizontal muscle layers
-top of uterus contracts bottom has to give way - cervix length becomes shorter as labour progresses and dilates and the cervix progressively gets thinner (effacement)
What regulates stimulation of contraction phase?
-prostaglandins
-oxytocin
- CRH - cortisol levels rise in mother when fetus is ready
-increased synthesis of cytokines
What is the difference between stimulation and activation?
stimulation = when contraction begins
activation = the process of labour happening itself
What hormonal changes occur in initiation of labour?
- closer to labour more sensitivity of myometrium to prostoglandin and oxytocin = increased responsiveness to oxytocin
progesterone levels decrease = progesterone involved in keeping the endometrium lining intact
-Increased Estrogen bio-availability
-CRH and neuro-endocrine mediators increase = increased cortisol - baby’s way of telling mother it is ready to come out
Exact mechanisms for initiation of labour is uncertain but believed to involve these hormones:
- Progesterone decrease
- Oestrogen increase
- Oxytocin increase
- Relaxin
- Inflammatory cytokines
- Nitric oxide increase
- Corticotrophin-releasing hormone / fetal cortisol levels high so increased levels in mother - indicates
- Prostaglandins - comes from “prostate” glands ,final common mediators of labour
- strong stimulants of labour and used to induce labour
How does progesterone maintain normal pregnancy and prevent pre- mature labour?
*Decreases myometrial contractility
* inhibits myometrial gap junction formation
* Stimulates uterine NO synthetase = less constriction and contractility
* Stimulates cAMP which inhibits intracellular calcium
in the sarcoplasmic reticulum (SR) = less contractility
* Down-regulates prostaglandin production,
development of calcium channels and oxytocin
receptors = all involved in inducing labour
* inhibits collagenolysis in the cervix by increasing tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)
- How is progesterone induce myometrial changes?
- does not fall pre labour - produced by placenta and corpus luteum
- however there is an up-regulation of pro-inflammatory (PR-A) and downregulation of anti-inflammatory hormone PR-B receptor activity resulting in functional progesterone withdrawl during labour
-prostaglandins synthesis , CRF secretion , interleukin synthesis , oestrogen receptors expression and oxytocin receptors affinity all inhibit progesterone = promoting contractility
-Prostaglandins degradation , PTH-rp synthesis
-CGRP secretion , CGRP and AM receptor expression all stimulate progesterone = decrease contraction
Why is increased PR-A/PR-B ratio a problem for clinicians?
- increased PR-A/PR-B ratio is linked with activation of nuclear factor kappaB(NF-kB) in the myometrium
-NF-kB increases expression of COX-2 and various pro- inflammtory cytokines (eg,. IL-8) which causes cervical ripening and upregulates oxygen receptor expression in the myometrium.
=> it is hard to distinguish if inflammatory factors are due to pregnancy or if it is due to infection in clinics
Where is oestrogen produced and what is its role in maintaining a pregnancy?
Estrogen
* Essential for uterine development & function
* The placenta is the primary source
* Placenta relies on DHEAS from the fetal & maternal adrenal glands for the supply of precursor for estrogen synthesis
* Both estrogen and progesterone increase towards term but the ratio of estrogen to progesterone begins to favor estrogen
- How does oestrogen induce myometrial and cervical changes in labour?
Myometrial :
* Mechanical stretch induced by by oestrogen
* Increase in the number of PG and Oxytocin
receptors
* Up-regulation of the enzymes responsible for
muscle contractions (myosin light chain
kinase, calmodulin)
* Increase in connexin-43 synthesis & gap
junction formation in the myometrium
Cervical:
* Induction of collagenase & elastase: Cervical
ripening
3 .How does oxytocin induce myometrial changes in labour?
-myometrial sensitivity increases near due date due to changes in affinity and density ( 200-300 fold).
-oxytocin receptor conc greatest in the fundus and minimal in lower segment
Myometrium
- increased intracellular Ca2+ levels
-myosin phosphorilation
-binding myosin- actin
= increased uterine contractions
Decidua :
- increased PGF2 alpha synthesis and secretion = increased uterine contractions
hypothetical model: cervical
initiation of labour summary
What are different phases of uterine activity?
How stress induces labour:
inflammation of the decidua induced changes in labour
Hemorhhage induced changes in labour
