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BIOMEDICAL SCIENCE YEAR 3 > labour > Flashcards

labour Flashcards

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1
Q

What is the transition in myometrium, cervix and membranes in successful labour between antenatal and intrapartum

A

Myometrium goes from quiescent to contractile
Cervix becomes open from closed
membranes go from intact to ruptured

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2
Q

describe actin myosin interactions in uterine contractility

A

Thin actin filaments going horizontally across
Thick myosin filaments in between vertically
During contraction the Z discs come closer together

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3
Q

There are 4 phases in labour- quiescence, activation, stimulation and initiation of labour. Describe the quiescence phase

A

• Progesterone
• PGI2
• Relaxin
• Parathyroid hormone-related peptide(PTHrP)
• Calcitonin gene-related peptide, vaso-active
intestinal peptide
• Nitric oxide(NO)
All these lead to increased intracellular (cAMP)or
(cGMP) which inhibit the release of intracellular
calcium for myometrial contractility

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4
Q

Describe the activation phase

A

Rise in estrogen and CRH
• Mechanical stretch
• up-regulation of a panel of genes required for
contractions: Connexin 43, prostaglandin and
oxytocin receptors (OTRs)

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5
Q

Describe the stimulation phase

A

Prostaglandins
• Oxytocin
• CRH
• Increased synthesis of cytokines

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6
Q

Describe initiation of labour

A 
Functional Progesterone withdrawal
• Increased Estrogen bio-availability
• CRH and neuro-endocrine mediators
• Increased responsiveness of the myometrium
to prostaglandins and oxytocin
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7
Q

Describe the role of progesterone in labour

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

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)

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8
Q

What does stimulation and inhibition of progesterone cause

A 
Stimulation:
prostaglandin secretion
PTH-rp synthesis
CGRP secretion
AM receptor expression
Inhibition:
Prostaglandin synthesis
CRF secretion
interleukin synthesis 
oestrogen receptor expression
oxytocin receptors affinity
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9
Q

Progesterone pathway affecting inflammatory factors

A

In most species, progesterone levels fall pre-labour
• This does not occur in humans, however there is
upregulation 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 proinflammatory cytokines (e.g. IL-8 and IL-1b), which
cause cervical ripening and up-regulate oxytocin
receptor expression in the myometrium

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10
Q

What is the role of oestrogen in labour

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

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11
Q

DHEAS to oestrogen

A

Foetus releases DHEA-S (from adrenals of mother and foetus)
3BHSD, aromatase, and 17BHSD
causes conversion into
oestradiol, oestriol, estron

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12
Q

oestrogen induced myometrial changes

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

oestrogen increases:
gap junction formation, oxytocin responsiveness, PG synthesis and release. All work together to increase uterine contractility

collegenase and elastase induction
causing cervical dilatation

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13
Q

Describe oxytocin in labour

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

• Receptor concentration greatest in the fundus and
minimal in the lower segment and cervix

• Oxytocin receptor upregulation is promoted by
oestrogen and mechanical stretch

• Increases inositol 1,4,5-triphosphate and intracellular Ca

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14
Q

Effect of oxytocin on the myometrium and decidua

A

Effect of oxytocin on myometrium:
Intracellular Ca2+ increased
causes myosin phosphorylation
increases actin-myosin

effect of oxytocin on decidua
PGF2alpha synthesis and secretion

both cause uterine contractions

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15
Q

Role of relaxin in labour

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

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16
Q

Effect of inflammatory cytokines in labour

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

17
Q

Effect of nitric oxide in labour

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 ê prior to onset of labour
• Cervical NO é at term, thus implicated in ripening

18
Q

Effect of CRH and cortisol

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

19
Q

Effect of uro-cortins

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

20
Q

Effect of prostaglandins

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
• 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

21
Q

Other factors affecting contractility and induction of labour

A

Epidermal growth factor – é PG levels, promotes
uterine contraction by increasing intracellular Ca
• Parathyroid hormone related peptide (PTHrP)
– has relaxant effect on myometrium (ê 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
• Oestrogen to progesterone ratio
• Engagement and descent of fetal head
(placing pressure on cervix)
• Neuroendocrine effects of cervical stretch, leading
to increase oxytocine release (“Ferguson’s reflex”)
• Altered uterine wall tension (myometrial stretch)
• Parasympathetic to sympathetic balance
• Hyaluronic acid levels
• Cervical stimulation (sexual intercourse / “sweep”)

22
Q

What are the major changes in the myometrium during initiation of labour

A

up Coupling
up Ion channels
up Receptors
down NO-system

up Conductivity
up Excitability
down Relaxation

Reinforcement
of contractions

23
Q

What are the major changes in the cervix during initiation of labour

A

Increased Inflammatory
response
Increased Collagenase

Increased Ripening

all cause Dilatation in successful labour

24
Q

What are the major changes in the membranes during initiation of labour

A

ECM
degradation
Reduced Tissue integrity

in successful there is rupture

25
Q

What are the phases of labour

A

Quiescence- phase 0

activation- phase 1

stimulation- phase 2- delivery happens (postpartum)

involution- phase 3

uterine activity is down the whole time and on the graph it curves upwards at phase 2

26
Q

Define labour

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”

First stage = onset to full cervical dilatation
(10cm)
• latent phase = 0–3cm
• active phase = from 4cm
• Second stage = full dilatation to delivery of the
foetus
• Third stage = delivery of foetus to delivery of
placenta

27
Q

Describe preterm birth

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 – cervical length / fetal fibronectin

• Causative/associated factors
Ø Infection
Ø Inflammation
Ø Maternal stress
Ø Intrauterine haemorrhage
Ø Uteroplacental insufficiency
(e.g. pre-eclampsia and fetal growth restriction)
28
Q

Summary

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

BIOMEDICAL SCIENCE YEAR 3 (29 decks)

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