Physiology of labour
Parturition: onset and mechanism of labour, oxytocin and prostaglandins
Labour starts when the forces that keep the uterus quiet (progesterone) are overcome by those that activate it (oestrogen, stretch, placental CRH, prostaglandins and oxytocin). The myometrium then contracts with fundal dominance and retraction while the fetus negotiates the pelvis by a set sequence of movements. CPSP asks about the endocrine trigger, the contraction mechanism, the cardinal movements and the pharmacology of uterotonics and tocolytics.
Keeping the uterus quiet
- Progesterone maintains myometrial quiescence and a closed cervix (vaginal progesterone for a short cervix in mid-pregnancy).
- In women progesterone levels stay high until the placenta is delivered: labour involves functional progesterone withdrawal (shift in progesterone receptor isoforms, local inactivation, inflammatory signalling). Blocking the receptor with mifepristone can start labour at any gestation.
Activating the uterus
- Rising oestrogen-to-progesterone effect induces contraction-associated proteins: oxytocin receptors (a very large rise at term), gap junctions (connexin 43) that couple cells, and prostaglandin synthesis. So a dose of oxytocin barely affects the uterus at 16 weeks but causes strong contractions at term.
- Placental CRH rises exponentially in late pregnancy and, unlike hypothalamic CRH, is stimulated by cortisol: a positive loop with the fetal adrenal (cortisol and DHEA sulphate for oestrogen). An unusually steep rise predicts preterm birth. Without a fetal HPA axis (anencephaly) pregnancy often goes far past 42 weeks.
- Stretch (twins, polyhydramnios) increases gap junctions and oxytocin receptors: preterm labour.
- Prostaglandins: at labour onset phospholipase A2 releases arachidonic acid; COX makes PGE2 (amnion) and PGF2-alpha (decidua). They ripen the cervix and stimulate contraction. Amniotomy releases local prostaglandins, so contractions often follow within an hour.
- Cervical ripening: collagen breakdown by enzymes, more hyaluronic acid and water, influx of inflammatory cells.
- Ferguson reflex: stretching of the cervix and vagina sends afferents to the hypothalamus, which releases more oxytocin: positive feedback.
Contraction mechanism
- Oxytocin receptor (Gq) activates phospholipase C: IP3 releases calcium from the sarcoplasmic reticulum and calcium also enters through L-type channels.
- Smooth muscle has no troponin: calcium binds calmodulin, activating myosin light-chain kinase; phosphorylation of myosin light chains lets actin and myosin cycle.
- Contractions start near the uterotubal junctions (pacemaker regions) and spread downward; they are strongest and longest at the fundus (fundal dominance), which pulls the lower segment and cervix up and dilates the cervix.
- Retraction: upper segment fibres relax after each contraction but do not return to full length, so the upper segment thickens and shortens while the lower segment thins. An exaggerated ridge between them in obstructed labour is a pathological retraction ring (Bandl's ring).
- Third stage: retraction shrinks the placental site and shears the placenta off through the spongy layer of the decidua basalis; criss-cross myometrial fibres then compress the vessels (living ligatures).
- Involution: the uterus falls from about 1,000 g to about 60 g in six weeks by autophagic shrinkage of each muscle cell, not loss of cells.
Mechanism of labour (left occipitoanterior)
| Movement | What happens |
|---|---|
| Engagement and descent | Widest transverse diameter passes the brim |
| Flexion | Presents the smallest diameter (suboccipitobregmatic) |
| Internal rotation | Occiput turns anteriorly under the symphysis, guided by the gutter of the pelvic floor |
| Extension | Head is born by extension as the occiput pivots under the symphysis |
| Restitution | Head untwists about 45 degrees back towards the side it came from (mother's left), realigning with the shoulders |
| External rotation | Shoulders rotate into the anteroposterior diameter; head turns further |
| Expulsion | Anterior shoulder under the symphysis, then the posterior shoulder and body |
- First stage active phase progresses at about 1 cm/hour; no cervical change for 4 hours despite adequate contractions is active-phase arrest.
Drugs acting on the uterus
| Drug | Mechanism and key point |
|---|---|
| Oxytocin | Gq receptor; rhythmic contractions; short half-life |
| Ergometrine | Alpha-adrenergic and 5-HT receptors; sustained tonic contraction; raises blood pressure (avoid in hypertension) |
| Carboprost (15-methyl PGF2-alpha) | FP receptor; bronchospasm: avoid in asthma |
| Misoprostol (PGE1) | Heat-stable, oral or rectal: useful without refrigeration |
| Atosiban | Oxytocin and vasopressin V1a receptor antagonist; few maternal side effects (suits heart disease) |
| Nifedipine | Blocks L-type calcium channels |
| Beta-2 agonists | Raise cAMP; tachycardia, hyperglycaemia |
| Indomethacin | COX inhibitor; reduces fetal renal blood flow and urine (oligohydramnios) and can constrict the ductus arteriosus |
Remember Oestrogen sets up the uterus (receptors and gap junctions); oxytocin and prostaglandins fire it.
Exam trap In women progesterone does not fall before labour; its action is withdrawn functionally.
Exam trap Ergometrine causes a sustained contraction and hypertension; oxytocin causes rhythmic contractions and hypotension when given as a bolus.
Test yourself on this topic
5 of the 26 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
An oxytocin infusion is started for augmentation of labour. Oxytocin binds a G protein-coupled receptor on myometrial cells. Which intracellular pathway mainly produces the contraction?
Answer: Gq, phospholipase C and IP3
The oxytocin receptor is coupled to Gq. Activated phospholipase C splits PIP2 into IP3 and diacylglycerol; IP3 releases calcium from the sarcoplasmic reticulum, and calcium also enters through voltage-gated channels. Calcium binds calmodulin and activates myosin light chain kinase, producing contraction. Oxytocin also stimulates decidual prostaglandin production. Drugs that raise cAMP or cGMP relax the myometrium.
Oxytocin receptor
- Gq coupled
- PLC makes IP3 and DAG
- IP3 releases calcium
- Calcium–calmodulin activates MLCK
Remember Oxytocin works through calcium, not cAMP.
Exam trap cAMP and cGMP relax the uterus; tocolytics work through them.
Why the other options are wrong
- Gs, adenylyl cyclase and cAMP Raises cAMP, which relaxes the uterus (beta-2 agonists).
- Gi, lower cAMP only Not the main pathway.
- Tyrosine kinase and MAP kinase Used by growth factors and insulin.
- Guanylyl cyclase and cGMP Mediates relaxation (nitric oxide).
Women with twin pregnancies or marked polyhydramnios are more likely to go into labour preterm, even when hormone levels are similar to those of singleton pregnancies. Which mechanism best explains this?
Answer: Stretch induces myometrial contraction proteins
Mechanical stretch of the myometrium is a signal for labour. Stretch increases expression of contraction-associated proteins such as oxytocin receptors and connexin 43 gap junctions, and stimulates prostaglandin production in the myometrium and membranes. An overdistended uterus therefore becomes excitable earlier. Progesterone normally opposes these changes, which is why its effect is outweighed in an overdistended uterus.
Stretch and labour
- Overdistension: twins, polyhydramnios
- More oxytocin receptors
- More gap junctions
- More prostaglandins
Remember A stretched uterus wakes up early.
Exam trap Hormones are only half the story; mechanical stretch also activates the uterus.
Why the other options are wrong
- Stretch lowers placental CRH output Placental CRH tends to be higher, not lower, with more placental mass.
- Stretch raises myometrial progesterone receptors Would favour quiescence.
- Stretch blocks oxytocin release Not an effect of stretch.
- Stretch closes myometrial gap junctions Stretch increases gap junctions.
A woman with heart disease in preterm labour at 30 weeks cannot take nifedipine or beta-agonists because of their cardiovascular effects. She is given an intravenous peptide tocolytic with few maternal side effects. How does it act?
Answer: Oxytocin receptor antagonist
Atosiban is a peptide analogue of oxytocin that competitively blocks oxytocin (and vasopressin V1a) receptors on the myometrium. It reduces IP3-mediated calcium release and the frequency of contractions. Because oxytocin receptors are concentrated in the uterus, it has few cardiovascular side effects, unlike nifedipine (hypotension, tachycardia) or beta-agonists (tachycardia, pulmonary oedema). It is used to delay delivery long enough for corticosteroids.
Tocolytics
- Atosiban: oxytocin antagonist
- Nifedipine: calcium channel blocker
- Terbutaline: beta-2 agonist
- Indomethacin: COX inhibitor
Remember Atosiban blocks oxytocin at its receptor.
Exam trap Tocolytics buy time for steroids; they do not improve outcome by themselves.
Why the other options are wrong
- Calcium channel blocker That is nifedipine.
- Beta-2 receptor agonist That is terbutaline or ritodrine.
- Cyclooxygenase inhibitor That is indomethacin.
- Nitric oxide donor That is glyceryl trinitrate.
During labour, the upper uterine segment becomes progressively thicker and shorter, while the lower segment becomes thinner. After each contraction the upper segment fibres relax but do not return to their original length. What is this property called?
Answer: Retraction
Retraction is a property of uterine muscle by which fibres shorten permanently after each contraction. It thickens the upper segment, reduces the volume of the uterine cavity, maintains progress between contractions and stretches the passive lower segment. After delivery, retraction keeps the uterus small and compresses the placental bed vessels. In obstructed labour, excessive retraction produces a pathological retraction ring and risks rupture of the thinned lower segment.
Retraction
- Fibres shorten permanently
- Upper segment thickens
- Lower segment thins
- Keeps uterus small after delivery
Remember Retraction holds the ground each contraction gains.
Exam trap Retraction is normal; a visible retraction ring signals obstruction.
Why the other options are wrong
- Contraction Contraction is temporary shortening that fully relaxes.
- Polarity Polarity describes the fundus-to-cervix gradient.
- Effacement Effacement is thinning of the cervix.
- Relaxation Relaxation is incomplete here.
Myometrium is smooth muscle and has no troponin. When intracellular calcium rises during a labour contraction, which event directly allows actin and myosin to interact?
Answer: Phosphorylation of myosin light chains
In smooth muscle, calcium binds calmodulin, and the complex activates myosin light chain kinase. MLCK phosphorylates the regulatory light chains of myosin, which enables cross-bridge cycling with actin. Myosin light chain phosphatase reverses this and causes relaxation. Tocolytic drugs act on this system: beta-2 agonists raise cAMP, which inhibits MLCK, and calcium channel blockers reduce calcium entry.
Smooth muscle contraction
- Calcium binds calmodulin
- Activates MLCK
- Myosin light chains phosphorylated
- Phosphatase relaxes
Remember Smooth muscle switches on myosin, not actin.
Exam trap Troponin is the calcium sensor in skeletal and cardiac muscle, not in the uterus.
Why the other options are wrong
- Calcium binding to troponin C Smooth muscle lacks troponin.
- Dephosphorylation of myosin by phosphatase This causes relaxation.
- Calcium binding to tropomyosin Calcium does not bind tropomyosin.
- Release of ATP from actin Not the mechanism.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Reproduction, pregnancy and labour, Parturition: onset and mechanism of labour, oxytocin and prostaglandins
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