Labour Flashcards
Define Labour (2)
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”
4 phases of pregnancy - labour: (4)
0 = quiescence
1= Activation
2= stimulation
3= involution
3 stages of Labour (3)
- First stage = onset to full cervical dilatation (10cm)
- latent phase = 0–3cm
- active phase = from 4cm
- Second stage = full dilatation to delivery of the fetus
- Third stage = delivery of fetus to delivery of placenta
Antenatal state: (3)
myometrium = Quiescent
Cervix = Closed
membranes = intact
Intrapartum state (labour): (3)
myometrium = contractile
cervix = open
membranes = Ruptured
How do you get successful labour - changes? (4)
Myometrium: inc. Coupling, Ion channels + Receptors, dec NO-system = inc. conductivity + excitability, dec. relaxation = REINFORCEMNT OF CONTRACTIONS
Cervix: inc. inflam response + collagenase = inc. ripening = DILATION
membranes: inc. ECM degradtion = dec. tissue integrity = RUPTURE
initiation - conditioning - active labour
Uterine contractility difference (2)
Skeletal muscle image
Contraction usually works: actin + myosin interaction = shortening
Myometrium is not skeletal/striated, it’s smooth. It doesn’t contracts and doesn’t cause retraction/relaxes. = constantly contracting to allow for baby to come out
Explains vertical and horizontal muscle layers of uterus.
There are these layers: contraction allows for progressive effacement of the cervix = thsi makes way for teh dilation of teh cervix = baby
Define effacement
The percentage shortening in the length of the surface and by the length of cervix
Quiescence phase - vasodila. (2)
Progesterone - promotes the maintainance of pregn.
(PGI2 - prostaglandin: relaxing/vasodil. = myometrium + vascular smooth muscle
Relaxin - vasodilation
PTHrP
Calcitonin
NO- smooth muscle relaxation)
All these lead to increased intracellular (cAMP) or (cGMP) which inhibit the release of intracellular calcium for myometrial contractility.
Activation phase - leads to stim. phase (going into labour) (3)
Rise in oestrogen and CRH
Mechanical strength ( > stretch = dec. pregn duration)
upreg. of a panel of genes required for contractions: PG & Oxytocin receptors (OTR’s) (posterior pituitary)
Stimulation phase (4)
- Prostaglandins
- Oxytocin
- CRH
- Increased synthesis of cytokines
Initiation of labour (4)
- Functional Progesterone withdrawal!!!!!!!!!! - levels don’t change
- Increased Estrogen bio-availability
- CRH and neuro-endocrine mediators
- Increased responsiveness of the myometrium to prostaglandins and oxytocin = recptors synth. + v sensitive @ end of pregn.
initiation: Exact mechanisms uncertain but believed to involve: (8)
- Progesterone
- Oestrogen
- Oxytocin
- Relaxin
- Corticotrophin-releasing hormone / fetal cortisol (placenta also releases)
- Nitric oxide
- Prostaglandins - prostate (semen story)
- Inflammatory cytokines
What % of women deliver on tehri due date?
6%
Progesterone background (3)
Is one of the main hormones of pregnancy
* Produced by corpus luteum in early pregnancy and the placenta later
* Cholesterol is converted to Progesterone by the action of P450scc and 3βHSD
Proges. MoA - given to miscarriage prone women(6)
- Decreases myometrial contractility
- Inhibits myometrial gap junction formation
- Stimulates uterine NO synthetase
- Stimulates cAMP and sequesters intracellular calcium in the sarcoplasmic reticulum (SR)
- Down-regulates prostaglandin production, development of calcium channels and oxytocin receptors
- inhibits collagenolysis in the cervix by increasing tissue inhibitor of matrix metalloproteinase-1 (TIMP-1)
Proges. 2 -like inflamm (4)
- In most species, progesterone levels fall pre-labour
- This does not occur in humans, however there is upreg. of (pro-inflammatory) PR-A, and suppression of (anti-inflammatory) PR-B receptor
activity, resulting in “functional” progesterone withdrawal - Increased PR-A/PR-B ratio is linked with activation of nuclear factor kappaB (NF-κB) in the myometrium
- NF-κB increases expression of COX-2 and various pro-inflammatory cytokines (e.g. IL-8 and IL-1b), which cause cervical ripening and up-regulate oxytocin receptor expression in the myometrium
Estrogen background: (4)
- 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
Estrogen-induced myometrial changes (4)
- Increase in the number of PG and OCT 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
- Induction of collagenase & elastase: Cervical ripening (re-labour ideal)
Oxytocin (4)
Synthesised in hypothalamus and released from posterior pituitary gland of mother, also produced by myometrium, decidua, placenta and
membranes
- Myometrial sensitivity to oxytocin increases near to term due to changes in density (up to 200-300 fold) and affinity of oxytocin receptors (even during labour - increased sensitivity)
- Receptor concentration greatest in the fundus and minimal in the lower segment and cervix
- Oxytocin receptor upregulation is promoted by oestrogen and mechanical stretch
What is the triplet descending gradient? (2)
Receptor concentration greatest in the fundus and minimal in the lower segment and cervix - if cervix contracts 1st + hardest = baby will not come out = strongest fundus + weakest at cervix
Relaxin (6)
- Insulin-like hormone produced by placenta and myometrium (corpus luteum in early pregnancy)
- Promotes myometrial quiescence in pregnancy
- Induces vasodilatation, skeletal muscle relaxation and renal adaptation to pregnancy
- Increases cAMP, inhibits calcium release in myocytes, decreases affinity of MLCK for calmodulin and myosin and activates K channels, thus hyperpolarising the muscle cell membrane
- Suppresses oxytocin release
- Enhances cervical ripening
Inflammatory Cytokines (5)
- Play a major role in enhancement of uterine contractility and cervical ripening
- Include IL-1, IL-6, IL-8, TNF-α, interferon and TGF-β
- All stimulate prostaglandin (PG) production in the myometrium, placenta and fetal membranes
- IL-8 also induces neutrophil chemotaxis/activation and production of matrix metalloproteinase (MMP)
- Inflammation outwith the uterus can also trigger labour e.g. surgical procedures, appendicitis, UTI - (sensitivity dependent at any stage)
Nitric Oxide (NO): (6)
- Produced by decidua, membranes, fetoplacental vascular endothelium and the syncytiotrophoblast
- Regulates vascular tone via release of prostacyclin
- Maintains myometrial quiescence
- Activates guanylate cyclase pathway, increases cGMP, decreases intracellular Ca concentrations
- Levels elevated in myometrium (but not cervix) during pregnancy and dec. prior to onset of labour
- Cervical NO inc. at term, thus implicated in ripening
Corticotrophin Releasing Hormone (CRH) and Cortisol (5)
- Extra CRH is produced by placenta and myometrium and levels increase 50–100 fold by late gestation
- CRH binding proteins fall towards term, increasing free (active) levels of CRH
- CRH inhibits PGE2, increases cAMP and upregulates NO synthase, promoting quiescence antenatally
- At term, however, CRH enhances the myometrial contractile response to PGF2α, PGE2 and oxytocin
- CRH stimulates the fetal adrenal gland to produce cortisol, which triggers conversion of progesterone to oestrogen – also promotes fetal lung maturation
CRH and ucorortins (5)
- Uro-cortins (Ucn,Ucn2,Ucn3) are structurally similar to CRH and show similar biological effects
- Are synthesized and secreted by placenta and fetal membranes
- Ucn levels remain relatively constant during gestation and increase only after onset of parturition
- Augment matrix metalloproteinase, ACTH and prostaglandin secretion
- Act as pro-inflammatory agents
Prostaglandins (PGs) (9)
- Final common pathway in labour onset mechanisms
- Produced in decidua and fetal membranes
- Stimulatory PGs (PGF2α, thromboxane, PGE1, PGE2) bind to the myocyte cell membrane, increase action potential frequency and stimulate contraction
- PGE2 plays a central role in cervical ripening
- PGF2α increases intracellular calcium / contractility (post-partum haemorrhage drug)
- Inhibitory PGs (PGD2 and PGI2) repress contraction
- PG levels are low and receptors down-regulated during pregnancy, and increase towards term
- Synthesis upregulated by NF-κB / COX-2 activation
water breaking = inc. PG’s (efficient initiation of labour) - one way system
Other factors 1 (4)
- Epidermal growth factor – inc. PG levels, promotes uterine contraction by increasing intracellular Ca
- Parathyroid hormone related peptide (PTHrP) – has relaxant effect on myometrium (dec. levels at term), also relaxes blood vessels and plays a role in placental calcium transport
- Magnesium – competes with calcium for calmodulin binding, reduces MLCK
- Endothelin – enhances myometrial contractility by increasing intracellular Ca / MLC phosphorylation, modulates fetoplacental circulation
Other factors 2 (7)
- Oestrogen to progesterone ratio
- Engagement and descent of fetal head (placing pressure on cervix)
- Neuroendocrine effects of cervical stretch, leading to increase oxytocin release (“Ferguson’s reflex”)
- Altered uterine wall tension (myometrial stretch)
- Parasympathetic to sympathetic balance
- Hyaluronic acid levels
- Cervical stimulation (sexual intercourse / “sweep”)
Pre-term birth (4)
- Delivery prior to 37 completed weeks gestation
- Affects between 7 to 11% pregnancies worldwide
- Predictive tests perform poorly but may be used in high risk groups – US cervical length / fetal fibronectin
- Causative/associated factors:
Infection
Inflammation
Maternal stress
Intrauterine haemorrhage
Uteroplacental insufficiency
(e.g. pre-eclampsia and fetal growth restriction)
What unconventional manner can you start labour in?
Sucking on the nipples - oxytocin
Stress, stress + haemorrhage +pre- term birth
images
Summary (3)
- Labour is a complex physiologic process involving fetal, placental, and maternal signals.
- A variety of endocrine systems play a role in the maintenance of uterine quiescence and the onset of labour (increase in uterine contractility and cervical ripening)
- There are many factors that can tip the balance between quiescence & contractile
