PHYSIOLOGY OF

LABOR
RIBKHI AMALIA PUTRI
GANOT SUMULYO

PREFACE

Extensive preparations in both

uterus and cervix long before last
few hours of pregnancy

Transitional phase myometrial

unresponsiveness is suspended, and
the cervix undergoes ripening,
effacement, and lost of structural
integrity

Labor onset culmination of

series of biochemical changes in
the uterus and cervix as the
result of endocrine and paracrine
signals emanating from both mother
and fetus

Abnormal parturition preterm

labor, dystocia, postterm pregnancy

Fetus
Fetus

Placenta
Placenta
Membranes
Membranes

Mother
Mother

PHASE OF
PARTURITION

Uterine Activity During Pregnancy

Progesterone
Prostacycline
Relaxin
Nitric Oxide
Parathyroid
hormone-related
peptide
CRH
HPL

Quiescence

Uterotrophins
Estrogen
Progesterone
Prostaglandins
CRH

Activation

Uterotonins
Prostaglandins
Oxytocin

Stimulation

2/23/16

Inhibitors

Involution
Oxytocin
Thrombin

Involution

Myometrial Action

Contraction greater
degree smooth muscle cell
shortening

Multiple directions

Not organized as skeletal

muscle

Regulation of Myometrial
Contraction and Relaxation

Actin-Myosin Interaction activates ATPase, hydrolyzes

ADP, generate force

Intracellular Calcium PGF2a and oxytocin receptors

Myometrial gap junctions

Cell Surface Receptors

Actin Myosin

Actin Myosin

Intracellular Calcium

Oxytocin receptor

Calcium channel

Extracellular
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Intracellular

Phospholipase C

cAMP
Ca+

+ Oxytocin
+ Prostaglandin

MLCK

Ca
store

Uterine contractions

Gap Junction

Uterus connexins 26,

40, 43, 45

Cell Surface
Receptors

CRHR1a and LH receptors

Phase
Phase11of
ofParturition:
Parturition:
Uterine
UterineQuiescence
Quiescenceand
and
Cervical
CervicalSoftening
Softening

Uterine Quiescence

Beginning even before implantation

Uterine smooth muscle tranquility
Uterus unresponsive until near the end of pregnancy
Uterus initiate size and vascularity extension to
accommodate pregnancy
Braxton Hicks or false labor

Cervical Softening

First palpable softening of lower uterine segment at 4-6

wga pregnancy diagnosis Hegar sign
Cervixs function during pregnancy:
1. Barrier protect from infection
2. Cervical competence despite increasing gravitational
forces
3. Extracellular matrix changes that allow progressive
increases in tissue compliance
. Structural changes:
. Increased vascularity, stromal hypertrophy, glandular
hypertrophy and hyperplasia, and slow, progressive
compositional or structural changes of extracellular matrix

Progestero
ne
promote expression of inhibitory
promote expression
of inhibitory
transcription
factor ZEB1zinc
transcription
factor homeobox
ZEB1zinc
finger
E-box binding
finger E-box
binding homeobox
protein
protein

inhibit expression of the

inhibit
expression
the
CAP
genes,
connexinof43,
CAP
genes, connexin
and oxytocin
receptor43,
and oxytocin receptor

bound to the progesterone

bound to
the recruit
progesterone
receptor
(PR),
receptor (PR),
recruitPSF
coregulatory
factors:
coregulatory factors:
PSF
polypyrimidine
tract binding
polypyrimidine tract
binding
protein-associated
splicing
factor
protein-associated
splicing
factor
and Sin3A/HDACsyeast switchand Sin3A/HDACsyeast
switchdependent3
homologue
dependent3
homologue
A/histone
deacetylase
A/histone deacetylase
corepressor
complex
corepressor complex

inhibit expression of the

inhibit
expression
of the
gene
encoding
the gap
gene encoding
junctional
proteinthe gap
junctional
connexin
43protein
connexin 43

Luteinizing Hormone
(LH) and Human
Chorionic
Gonadotropin (hCG)
Receptors

activate adenylyl cyclase by

activate
adenylyl
cyclase by
way
of a plasma
membrane
way of a plasma membrane
receptorGs-linked
receptorGs-linked

decreases contraction
decreases contraction
frequency and force
frequencythe
and
force of
decreases
number
decreases the number of
tissue-specific
tissue-specific
myometrial
cell gap
myometrial cell gap
junctions
junctions

Relaxin

H1 gene
decidua, trophoblast, and
prostate
H2 gene corpus luteum

mediates lengthening of
mediates lengthening of
the pubic ligament,
the pubic
ligament,
cervical
softening,
cervical
softening,
vaginal
relaxation
vaginal relaxation
inhibition
of myometrial
inhibition of myometrial
contractions
contractions

Atrial and Brain

Natriuretic Peptides
and Cyclic Guanosine
Monophosphate
(cGMP)

Activation of guanylyl
Activation
of guanylyl
cyclase
increases
cyclase increases
intracellular
cGMP levels
intracellular cGMP levels

promotes smooth muscle

promotes smooth muscle
relaxation
relaxation

Beta-Adrenoreceptors

cAMP signaling
cAMP signaling

promotes smooth muscle

promotes smooth muscle
relaxation
relaxation

Phase
Phase22of
ofParturition:
Parturition:
Preparation
Preparationfor
forLabor
Labor

Uterine Changes

Uterine awakening or activation

Progression of uterine changes during 6-8 wga

Increase of contracted-associated protein (CAPs) oxytocin

receptor, PGF receptor, and connexin 43 increase uterine
irritability and responsiveness to uterotonins

Formation of lower uterine segment from the isthmus

fetal head often descends to or even though the pelvic inlet.

Cervical Changes

Cervical ripening

Transition from the softening to ripening, begins weeks

or days before onset of contraction

Total amount and composition of proteoglycans and

glycosaminoglycans within the matrix are altered

Stromal invasion with inflammatory cells ervical

chemottractants attract inflammatory cells release
protease degradation of collagen and other matrix
component

Fibril size and packing are regulated by small protegoglycan such as

decorin that bind collagen.
Before cervical ripening, fibril size is uniform, and fibrils are well packed
and organized. During cervical ripening, fibril size is less uniform, and
spacing between collagen fibrils and fiber is increased and disorganized

Hormonal Changes

Progesteron withdrawl

Oxcytosin activation increased phospholipase C activity and

subsequent increases in cytosolic calcium levels and
uterine contractility

Phase
Phase33of
ofParturition:
Parturition:
Labor
Labor

Phase 3: Uterine Stimulation

Oxytocin
Receptors strikingly increases in myometrial and decidual
tissues near the end of gestation
Acts on decidual tissue to promote prostaglandin release
Synthesized directly in decidual and extraembryonic fetal
tissues and in the placenta

Prostaglandin
levels of prostaglandinsor their metabolitesin amnionic fluid,
maternal plasma, and maternal urine are increased during labor
the receptor level for PGF2 is increased in the decidua at term,
and this increase most
The fetal membranes and placenta also produce prostaglandins.
Primarily PGE2, but also PGF2,

Phase 3: Uterine Stimulation

Corticotropin-Releasing Hormone
(CRH)

Synthesized in the placenta and hypothalamus.

CRH plasma levels increase dramatically during the final 6 to 8
weeks
[Ca2+]i is increased by CRH activation of G proteins Gq and Gi
and leads to stimulation of IP3 production and increased
contractility

Endothelin-1
21-amino acid peptides that powerfully induce myometrial
contraction
expressed in smooth muscle and effects an increase in
intracellular calcium
Endothelin-1 is produced in myometrium of term gestations
Able to induce synthesis of other contractile mediators such as
prostaglandins and inflammatory mediators

Phase 3: Uterine Stimulation

Angiotensin II

Angiotensin II binding to the plasma-membrane

receptor evokes contraction

Two G-protein-linked angiotensin II receptors expressed

in the uterusAT1 and AT2. In nonpregnant women,
the AT2 receptor is predominant, but the AT1 receptor
is preferentially expressed in pregnant women

Stages of
Labor
Divided into three
stages:

First stage onset

of labor to
complete dilatation

Latent phase

Active phase

Second stage
fetal expulsion

Third stage
placental
separation and
expulsion

First Stage of Labor:

Clinical Onset of Labor

Forceful uterine contractions that effect delivery

begin suddenly

Labor initiation spontaneous release of a

small oc blood-tinged mucus from the vagina
bloody show

Uterine Labor Contraction

Interval gradually diminished from approximately 10 minutes

at onset of first stage labor to 1 minutes or less in the second
stage
Unremitting contractions uteroplacental blood flow
sufficiently to cause fetal hypoxemia
Duration 30-90 seconds, average 1 minute generate
amniotic fluid pressure at 20-60 mmHg (average 40 mmHg)

Pain of contraction:
Hypoxia of the contracted myometrium
Compression of nerve ganglia in the cervix and lower uterus
by contracted interlocking muscle bundles
Cervical stretching during dilatation
Stretching of the peritoneum overlying the fundus

Distinct of Upper and

Lower Uterine Segment
Upper segment:
Firm
Contracts, retracts, and expels the
fetus
Myometrium dosent relax to
original length after contraction
diminished content, but constant
tension
Uterine cavity become slightly
smaller with each contraction
progressively thickened
Lower segment:
Softer, distended, more passive
Softened and dilated greatly
expanded, thinned-out the tube
fetus can be pass

Distinct of Upper and

Lower Uterine Segment

Centrifugaal pull is exerted on

the cervix and creates
cervical dilatation

Pressure to the membrane

hydrostatic action of amnion
sac dilates the cervical
canal

Changes in Uterus Shape During Labor elongation

of the ovoid uterine shape and decrease horizontal
diameter increase fetal axis pressure, straighten
fetal vertebral column

Ancillary Forces in labor maternal intraabdominal

pressure as pushing

Cervical Changes

Effacement and
dilatation occur in
the already-ripened
cervix

Effacament
shortening of
cervical canal 2 cm
to circular orifice.
Muscular fiber at
the level internal
cervical os are
pulled into the
lower segment of
uterus

Second Stage of Labor: Fetal

Descent

Cardinal Movements of Labor

Engangement

Descent

Flexion

Internal rotation

Extension

External rotation

Expulsion

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42

Third Stage of Labor: Delivery of

Placenta and Membranes

Contraction of uterus diminishing size decrease

area of placental implantation site

Increased placental thickness and limited elasticity

tension pulls the weakest layer (decidua)

Membranes are peeled off the uterine wall by

further contraction of myometrium and traction

Phase
Phase44of
ofParturition:
Parturition:
The
ThePuerperium
Puerperium

Myometrium in state rigid and persistent contraction

and retraction

Directly compresses large uterine vessels and allows

thrombosis prevent hemorrhage

Onset of lactogenesis

Reinstitution of ovulation signal 4-6 weeks after

birth

Fetal Contributions

Fetal Endocrine Cascades Leading to

Parturition

From the fetal hypothalamic-pituitary-adrenal axis

Placental Corticotropin-Releasing Hormone

Production

Synthesized in large amount

Stimulate by cortisol
Placental CRH may enhance fetal cortisol production to
provide positive feedback so that the placenta
produces more CRH
Stimulate fetal adrenal C19-steroid synthesis, thereby
increasing substrate for placental aromatization shift
the expression of a series of myometrial contractile
proteins

Fetal Lung
Surfactant

Surfactant protein A (SP-A) produced by the fetal lung is

required for lung maturation
Increased in amnionic fluid at term activate fluid
macrophages to migrate into the myometrium and
induce NF-B

Fetal Anomalies and Delayed

Parturition

fetal anencephaly fetal brain-pituitary-adrenal

function

adrenal hypoplasia

Intrauterine Tissues
Contributions

Amnion

Tensile strengthresistance to tearing and ruptureof

the fetal membranes

Several bioactive peptides and prostaglandins that cause

myometrial relaxation or contraction are synthesized in
amnion

Chorion Laeve

Enzymes include prostaglandin dehydrogenase (PGDH),

oxytocinase, and enkephalinase

Decidua
Decidual uterotonins that act in a paracrine on contiguous
myometrium
Expresses steroid metabolizing enzymes such as 20-HSD and
steroid 5R1 that may regulate local progesterone withdrawal
Decidual activation is characterized by increased
proinflammatory cells and increased expression of
proinflammatory cytokines, prostaglandins, and uterotonins
such as oxytocin receptors and connexin 43
Cytokines produced in the decidua can either increase
uterotonin production

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References

William Obstetric 24th Edition

Creasy & Resniks Maternal-Fetal Medicine

Steven Gabbe, Obstetric Normal and Problem