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Science of Repro > Labour > Flashcards

Labour Flashcards

1
Q

Define Labour (2)

A

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”
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2
Q

4 phases of pregnancy - labour: (4)

A

0 = quiescence
1= Activation
2= stimulation
3= involution

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3
Q

3 stages of Labour (3)

A
  • 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
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4
Q

Antenatal state: (3)

A

myometrium = Quiescent
Cervix = Closed
membranes = intact

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5
Q

Intrapartum state (labour): (3)

A

myometrium = contractile
cervix = open
membranes = Ruptured

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6
Q

How do you get successful labour - changes? (4)

A

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

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7
Q

Uterine contractility difference (2)

A

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

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8
Q

Explains vertical and horizontal muscle layers of uterus.

A

There are these layers: contraction allows for progressive effacement of the cervix = thsi makes way for teh dilation of teh cervix = baby

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9
Q

Define effacement

A

The percentage shortening in the length of the surface and by the length of cervix

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10
Q

Quiescence phase - vasodila. (2)

A

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.

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11
Q

Activation phase - leads to stim. phase (going into labour) (3)

A

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)

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12
Q

Stimulation phase (4)

A
  • Prostaglandins
  • Oxytocin
  • CRH
  • Increased synthesis of cytokines
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13
Q

Initiation of labour (4)

A
  • 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.
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14
Q

initiation: Exact mechanisms uncertain but believed to involve: (8)

A
  1. Progesterone
  2. Oestrogen
  3. Oxytocin
  4. Relaxin
  5. Corticotrophin-releasing hormone / fetal cortisol (placenta also releases)
  6. Nitric oxide
  7. Prostaglandins - prostate (semen story)
  8. Inflammatory cytokines
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15
Q

What % of women deliver on tehri due date?

A

6%

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16
Q

Progesterone background (3)

A

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

17
Q

Proges. MoA - given to miscarriage prone women(6)

A
  • 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)
18
Q

Proges. 2 -like inflamm (4)

A
  • 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
19
Q

Estrogen background: (4)

A
  • 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
20
Q

Estrogen-induced myometrial changes (4)

A
  • 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)
21
Q

Oxytocin (4)

A

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
22
Q

What is the triplet descending gradient? (2)

A

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

23
Q

Relaxin (6)

A
  • 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
24
Q

Inflammatory Cytokines (5)

A
  • 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)
25
Q

Nitric Oxide (NO): (6)

A
  • 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
26
Q

Corticotrophin Releasing Hormone (CRH) and Cortisol (5)

A
  • 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
27
Q

CRH and ucorortins (5)

A
  • 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
28
Q

Prostaglandins (PGs) (9)

A
  • 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

29
Q

Other factors 1 (4)

A
  • 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
30
Q

Other factors 2 (7)

A
  • 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”)
31
Q

Pre-term birth (4)

A
  • 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)
32
Q

What unconventional manner can you start labour in?

A

Sucking on the nipples - oxytocin

33
Q

Stress, stress + haemorrhage +pre- term birth

A

images

34
Q

Summary (3)

A
  • 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

Science of Repro (32 decks)

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