Chapter 21: PHYSIOLOGY OF LABOR

CHAPTER OUTLINE LABOR

o Refer to the last few hours of pregnancy
o Characterized by forceful and painful uterine contractions that effect cervical dilation
A. MATERNAL AND FETAL COMPARTMENTS o Cause the fetus to descend through the birth canal
a) Uterus
b) Placenta PARTURITION: Bringing forth of the young
B. SEX STEROID HORMONE ROLE 3 THEORIES THAT DESCRIBE LABOR INITIATION:
C. PROSTAGLANDINS ROLE 1) Functional loss of pregnancy maintenance factors
D. PHASE 1: UTERINE QUIESCENCE AND CERVICAL SOFTENING 2) Synthesis of factors that induce parturition
a) Myometrial relaxation and contraction 3) Mature fetus is the source of the initial signal for parturition commencement
✓ Actin-myosin interactions
CONSEQUENCES OF ABNORMAL PARTURITION:
✓ Regulation of membrane potentials
o Preterm labor
✓ Myometrial gap junctions
o Dystocia
✓ Endoplasmic reticulum stress response
o Post-term pregnancy
✓ G-protein-coupled receptors
✓ Cyclic guanosine monophosphate
✓ Accelerated uterotonin degradation
b) Decidua MATERNAL AND FETAL COMPARTMENTS
c) Cervical softening
E. PHASE 2: PREPARATION FOR LABOR
UTERUS
a) Progesterone withdrawal MYOMETRIUM
b) Myometrial changes o Composed of bundles of smooth muscles surrounded by connective tissue
✓ Oxytocin receptors o Phenotypic plasticity:
c) Cervical ripening • Smooth muscle cells are not terminally differentiated
✓ Cervical connective tissue • Readily adaptable to environmental changes (e.g., mechanical stretch, inflammation, signals)
= Collagen o Several smooth muscle qualities confer advantages for uterine contraction efficiency and fetal delivery:
= Glycosaminoglycans and proteoglycans • Greater degree of muscle cell shortening with contractions
= Inflammatory changes • Forces can be exerted in multiple directions
✓ Induction of cervical ripening • Plexiform arrangement – thin and thick filaments found in long, random bundles
✓ Endocervical epithelia • Greater multidirectional force generation in the uterine fundus compared with that of the lower uterine
d) Fetal contributions to parturition segment – permits versatility in expulsive force directionality
✓ Uterine stretch
✓ Fetal endocrine cascades ENDOMETRIUM (DECIDUA)
✓ Fetal lung surfactant and PAF o Composed of stromal cells and maternal immune cells
✓ Fetal-membrane senescence o Maintains pregnancy by unique immunoregulatory functions that suppress inflammatory signals during gestation
F. PHASE 3: LABOR o At the end of pregnancy:
a) First stage: clinical onset of labor • Decidual activation ensues
✓ Uterine labor contractions • Transitions to induce inflammatory signals
✓ Cervical changes • Withdraw active immunosuppression to contribute to parturition initiation
b) Second stage: fetal descent CERVIX
c) Pelvic floor changes o Functions during pregnancy:
d) Third stage: delivery of placenta and membranes • Maintenance of barrier function to protect the reproductive tract infection
e) Uterotonins in phase 3 • Maintenance of cervical competence despite greater gravitational forces as the fetus grows
✓ Oxytocin • Orchestration of extracellular matrix changes that allow progressively greater tissue compliance
✓ Prostaglandins o By the end of the pregnancy:
✓ Endothelin-1 • Cervix is distensible
✓ Angiotensin II • Consistency is similar to the lips of the oral cavity
G. PHASE 4: THE PUERPERIUM • Cross-sectional area of cervical canal and stroma increases
• Cervical epithelia proliferate

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR
PLACENTA o 15-hydroxyprostaglandin dehydrogenase (PDGH)
• Control metabolism of prostaglandins
FUNCTIONS: • Expression is upregulated during pregnancy in the uterus and cervix
o Providing the exchange of nutrients and waste between mother and fetus • Ability to rapidly inactivate prostaglandins
o Key source of steroid hormones, growth factors, and other mediators that maintain pregnancy and aid transition o Myometrial responses to prostaglandins stem from:
to parturition • Balance between prostaglandin synthesis vs. metabolism
FETAL MEMBRANES: • Relative expression of various prostaglandin receptors
o Include the amnion and chorion and adjacent decidua • Switch in receptor-signaling pathways
o Make up an important tissue shell around the fetus o Prostanoids contribute to myometrial relaxation at one stage of pregnancy and to myometrial contractions after
o Serves as a physiological, immunological, and metabolic shield to protect against untimely parturition initiation parturition initiation
o Amnion
PROSTAGLANDINS FROM THE AMNION
• Provides tensile strength to resist membrane tearing and rupture
o Late in pregnancy, amniotic prostaglandin biosynthesis is increased
• Avascular tissue – highly resistant to penetration by leukocytes, microorganisms and neoplastic cells o Phospholipase A2 and PGHS-2 show greater activity
• Constitutes a selective filter to prevent fetal particulate-bound lung and skin secretions from reaching o Amnion is likely the major source for amniotic fluid prostaglandins
the maternal compartment → protect maternal tissues from amniotic fluid constituents that could o Plays role in the activation of cascades that promote membrane rupture
prematurely accelerate decidual or myometrial activation o Prostaglandin transport from the amnion through the chorion to access maternal tissues is limited by PDGH
o Chorion
• Primarily protective tissue layer
•
•
Provides immunological acceptance
Enriched with enzymes that inactivate uterotonins
PHASES OF PARTURITION
✓ Uterotonins = agents that stimulate contractions
✓ Inactivating enzymes = prostaglandin dehydrogenase, oxytocinase, enkephalinase

SEX STEROID HORMONE ROLE

ESTROGEN PROGESTERONE
• Promotes parturition • Inhibits the events leading to parturition
• Aids processes that mediate uterine activation • Progesterone withdrawal
and cervical ripening ✓ Directly precedes progression of
• However, it can advance progesterone parturition
responsiveness and promote uterine ✓ Administration of progesterone -receptor
quiescence antagonists (e.g., mifepristone,
• Receptors: ERα and ERβ onapristone) will promote some key
features of parturition
• Receptors: PR-A and PR-B

PROSTAGLANDINS ROLE
FUNCTIONS:
o Lipid molecules with varied hormone-like actions
o Play a role in myometrial contractility, relaxation, and inflammation
o Interact with a family of 8 different G-protein-coupled receptors expressed in myometrium and cervix
MAJOR SYNTHETIC PATHWAYS INVOLVED IN PROSTAGLANDIN BIOSYNTHESIS:
o Produced from arachidonic acid
• Plasma membrane-derived
• Released by the action of phospholipase A2 or C
o Type 1 and 2 prostaglandin H synthase (PGHS-1 and -2)
• Other name: cyclooxygenase-1 and -2 (COX)
• Convert arachidonic acid to the unstable prostaglandin G2 → prostaglandin H2
o Prostaglandin isomerase
• Convert prostaglandin H2 to active prostaglandins (PGE2, PGF2α, PGI2)
• Expression is tissue-specific

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR

PHASE 1: UTERINE QUIESCENCE AND CERVICAL SOFTENING MYOMETRIAL GAP JUNCTIONS

o Gap junctions – aid the passage of electrical or ionic coupling currents as well as metabolite coupling
o Myometrial quiescence is imposed beginning before implantation and continues until the near end of pregnancy o Consist of connexons (hemi-channels), each composed of 6 connexin subunits
o This phase comprises 95% of pregnancy o Connexin-43 – is expressed in myometrium; concentrations rise near labor onset
o Characterized by: o Contraction-associated proteins (CAPs)
• Uterine smooth muscle tranquility • Include:
• Maintenance of cervical structural integrity ✓ Oxytocin receptor
• All manner of molecular systems are called to implement and coordinate a state of unresponsiveness ✓ Prostaglandin F receptor
o Complementary “fail-safe” system to protect the uterus against agents that could perturb the tranquility ✓ Connexin-43
o Myometrial cells undergo phenotypic modification to a noncontractile state but also initiate extensive changes • Progesterone lowers expression of these proteins to maintain quiescence
in its changes in its size and vascularity to accommodate fetal growth and prepare for uterine contractions ✓ Released inhibition = greater uterine contractility
• Increased stretch + greater estrogen dominance raises their levels
BRAXTON HICKS CONTRACTIONS (FALSE LABOR) ENDOPLASMIC RETICULUM STRESS RESPONSE
o Low-intensity myometrial contractions felt during the quiescent phase o Caspase 3 – anti-contractile agent; degrades both actin and connexin-43
o Normally do not cause cervical dilation o Endoplasmic reticulum stress response (ERSR)
o Common toward the end of pregnancy especially in multiparas • Unfolded-protein response
QUIESCENCE OF PHASE 1 STEMS FROM: • Regulate myometrial caspase 3 activation
o Actions of estrogen and progesterone via intracellular receptors • Work to maintain homeostasis in the face of stimuli (stretch and inflammation) → promote caspase 3
o Myometrial-cell plasma membrane receptor-mediated increases in cAMP activation to preserve quiescence
o Generation of cGMP G-PROTEIN-COUPLED RECEPTORS
o Other systems (e.g., modification of myometrial cell ion channels)
Gαs-mediated activation of adenylyl cyclase Gαq-protein-mediated activation of phospholipase C
MYOMETRIAL RELAXATION AND CONTRACTION • Act with sex steroid hormones to maintain uterine • Releases arachidonic acid
quiescence/relaxation • Augment intracellular Ca2+ and contractility
RELAXATION CONTRACTILITY • AC prevents increased intracellular Ca2+ • Examples:
• Diminished intracellular crosstalk and • Enhanced interactions between the actin • Examples: ✓ Prostaglandin E receptors 1 and 3
reduced intracellular Ca2+ levels and myosin proteins ✓ LH-hCG receptors ✓ CRHR1 (during parturition onset)
• Ion-channels regulation of cell • Heightened excitability of individual ✓ CRH receptor (CRHR1) – during pregnancy
membrane potential myometrial cells ✓ β-adrenoreceptors
• Activation of the uterine ER stress- • Promotion of intracellular crosstalk that ✓ Prostaglandin E receptors 2 and 4
unfolded protein response allows synchronous contractions to ✓ Relaxin family peptide receptor (RXFP1)
• Uterotonin degradation develop
o β-adrenoreceptors
ACTIN-MYOSIN INTERACTIONS • Myometrial cell relaxation
o Relaxation – promotion of actin into a globular form • Rate limiting factors: number of receptors expressed, level of AC expression
o Contraction – actin is in fibril form; actin must be attached to the cytoskeleton for tension to develop • Agents binding to these are used for tocolysis of preterm labor (ritodrine, terbutaline)
o Role of calcium: o LH-hCG receptors
• Activates myosin light-chain kinase needed in actin-myosin coupling • Myometrial relaxation
• Uterine relaxation = promoted by low [Ca2+]i • Levels during pregnancy are greater before than during labor
• Uterine contraction = promoted by high [Ca2+]I; opening of voltage-gated ion channels allow additional • Lessens contraction frequency and force
calcium ions into the cell • Lowers the number of tissue-specific myometrial cell gap junctions
o Myosin phosphatase o Prostaglandin E receptors
• Enzyme which dephosphorylates myosin • Expressed in the myometrium during pregnancy and with labor onset
• Inhibition of this enzyme prolongs contraction • EP2 and EP4 – myometrial relaxation (during pregnancy)
• EP1 and EP3 – myometrial contractility (during labor)
REGULATION OF MEMBRANE POTENTIALS
o Relaxin family peptide receptor 1 (RXPF1)
o Before labor – myocytes maintain high interior electronegativity
• Myometrial relaxation
o Relaxation = maintenance of hyperpolarized membrane potential
• H1 relaxin gene
o Ca2+-activated K channel (BKCa)
✓ Expressed in decidua, trophoblast, prostate
• Plays dual and opposing roles to maintain balance between quiescence and contractility
• H2 relaxin gene
• Abundantly expressed in the myometrium
✓ Expressed in corpus luteum
• If open – K+ leaves the cell to maintain interior electronegativity = relaxation
✓ Origin of relaxin in plasma of pregnant women; peak between 8-12 week’s gestation
• If inhibited = contractility
✓ Decline to lower levels that persist until term

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR
o Corticotropin-releasing hormone receptor (CRHR1)
• Myometrial quiescence during most of pregnancy but then aids in contractions with parturition onset PHASE 2: PREPARATION FOR LABOR
• Expressed in placenta and hypothalamus o Uterine awakening or activation – myometrial tranquility of phase 1 is suspended
• Plasma levels rise during the final 6-8 weeks of normal pregnancy o Progression of uterine changes during the last few weeks of pregnancy
CYCLIC GUANOSINE MONOPHOSPHATE o Shifting events associated with this phase can cause either preterm or delayed labor
o Activation of guanylyl cyclase increases cGMP
o Promotes smooth muscle relaxation PROGESTERONE WITHDRAWAL
o Increased in pregnant myometrium
o Stimulated by: o Classic progesterone withdrawal resulting from decreased secretion does not occur in human parturition
• Atrial natriuretic peptide (ANP) o Progesterone inactivation
• Brain natriuretic peptide (BNP) receptors • Myometrium and cervix become refractory to progesterone’s inhibitory actions
• Nitric oxide • Mifepristone
✓ Classic antagonist acting at progesterone receptor
ACCELERATED UTEROTONIN DEGRADATION
✓ Have some effect on cervical ripening and increasing myometrial sensitivity to uterotonins
o Activity of enzymes that degrade or inactivate uterotonins are strikingly increased in phase 1
✓ Less effective in inducing abortion or labor in women later in pregnancy
o Levels of some of these enzymes decrease late in gestation
o Multiple mechanisms exist for withdrawal or antagonism:
Degrading enzyme Uterotonin • Changes in the relative expression of PR-A, PR-B, and PR-C
15-hydroxyprostaglandin dehydrogenase (PDGH) Prostaglandins • Differential interaction of PR-A and PR-B with enhancers and inhibitors of gene expression
• Alterations in PR activity through changes in the expression of coactivators or corepressors that directly
Enkephalinase Endothelin
influence receptor function
Oxytocinase Oxytocin • Local inactivation of progesterone by steroid-metabolizing enzymes or synthesis of a natural antagonist
Diamine oxidase Histamine • MicroRNA regulation of progesterone-metabolizing enzymes and transcription factors that modulate
uterine quiescence
Catechol O-methyltransferase Catecholamines
Angiotensinase Angiotensin-II MYOMETRIAL CHANGES
PAF acetylhydrolase Platelet-activating factor
o Prepare the myometrium for labor contractions
o Shift in the expression of key proteins for uterine quiescence → expression of contraction-associated proteins
DECIDUA o Increase in number of oxytocin receptors and connexin-43
o Increase uterine irritability and responsiveness to uterotonins
o To ensure uterine quiescence: o Formation of the lower uterine segment from the isthmus
• Synthesis of PGF2α is markedly suppressed • Lightening – fetal head descends to or through the pelvic inlet
• Suppression withdrawal is prerequisite for parturition • Abdomen undergoes a shape change (“the baby dropped”)
o To promote immune tolerance (protect the fetus): • Elevated expression of the HoxA13 gene in lower myometrial segment compared with the upper segment
• Decidual stromal cells proactively ensure that fetal antigens do not elicit a maternal immune response
• Reduced capacity to attract T cells OXYTOCIN RECEPTORS
• Epigenetic silencing of T cell-attracting inflammatory chemokine genes o Levels rise during phase 2
o Level of oxytocin receptor mRNA at term is greater than that found in preterm myometrium
CERVICAL SOFTENING o Expression is regulated by progesterone and estradiol
• Estradiol – raises concentration
o Refers to the initial stage of cervical remodeling • Progesterone – enhance degradation and inhibit activation
o Greater tissue compliance, yet the cervix remains firm and unyielding
o Palpable softening of the lower uterine segment at 4 to 6 weeks’ gestation CERVICAL RIPENING
o Results from:
• Increased vascularity o Second phase of cervical remodeling
• Cellular hypertrophy and hyperplasia o Refer to connective tissue changes in the cervix to prepare for yielding and dilating during uterine contractions
• Slow, progressive compositional and structural changes in the ECM o Transition from softening to ripening begins weeks or days before labor
o Collagen o Cervix changes its total amounts of glycosaminoglycans and proteoglycans
• Main structural protein in the cervix CERVICAL CONNECTIVE TISSUE
• Undergoes conformational changes that alter tissue stiffness and flexibility
• Mature cross-links between newly synthesized collagen monomers are reduced • Type I, III, and IV
• Diminished expression and activity of crosslink-forming enzymes (lysyl hydroxylase, lysyl oxidase) Collagen • Largely responsible for the structural disposition of the cervix
o Genes involved in cervical dilation and parturition are actively repressed • Cross-linkage, fibril size, packing, and organization determine strength
and mechanical properties of cervix

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR
• These properties are regulated by: decorin, biglycan, thrombospondin 2 o Corticotropin-releasing hormone (CRH)
• Higher turnover during pregnancy ✓ Enhance fetal cortisol production
✓ Allows gradual replacement of mature cross-linked collagen ✓ Augment myometrial contractile force in response to PGF2α
fibrils with poorly cross-linked fibrils ✓ Stimulates fetal adrenal C19-steroid synthesis to increase substrate for placental
✓ Yield greater collagen disorganization aromatization
• Hyaluronan • Synthesized by the placenta in large amounts
✓ high MW polysaccharide that functions alone • Cortisol stimulates placental production (feed-forward cascade that does not end until delivery)
✓ hydrophilic, space-filling molecule • Levels rise in the last 12 weeks of pregnancy → peak during labor → then fall precipitously after
✓ greater production = increased viscoelasticity, hydration, delivery
Glycosaminoglycans and and matrix disorganization • Concentrations also rise in amniotic fluid
proteoglycans ✓ hyaluronan synthase isoenzymes – elevated during ripening • CRH-binding protein (CRH-BP)
• Proteoglycans ✓ Binds most maternal circulating CRH and inactivates it
✓ Formed by glycosaminoglycan-protein complexes ✓ In later pregnancy, levels decline → greater levels of bioavailable CRH
✓ 3 small leucine-rich proteoglycans are expressed in the cervix • CRH receptor
1) Decorin ✓ Favors switch from cAMP formation to increased calcium levels via a protein kinase C
2) Biglycan activation
3) Fibromodulin • Fetal-placental clock
✓ Also expressed in the fetal membranes and uterus ✓ Rising CRH level at the age of gestation
Inflammatory changes • Resident immune cells are localized to the cervical stroma ✓ Rate of rise in maternal CRH is a more accurate predictor of pregnancy outcome
• Leukocyte migration but not activation takes place before labor
FETAL LUNG SURFACTANT AND PAF
INDUCTION OF CERVICAL RIPENING o Surfactant protein A (SP-A)
o Direct application of prostaglandins PGE2 and PGF2α • Produced by the fetal lung for maturation
o This treatment modifies ECM structure to aid ripening • Expressed by the human amnion and decidua; present in amniotic fluid
o Administration of progesterone antagonists • Uterotonic agent
✓ Prompts signaling pathways in human myometrial cells
ENDOCERVICAL EPITHELIA ✓ Has effects on prostaglandins
o Epithelial cells proliferate such that endocervical glands account for a significant percentage of cervical mass ✓ Inhibits prostaglandin F2α in the term decidua
o Cells form a mucosal barrier and tight junctional barrier to protect against microbial invasion
✓ Levels drop in the amniotic fluid at term
o Platelet activating factor
FETAL CONTRIBUTIONS TO PARTURITION • Another uterotonic agent produced by the fetal lung
o The fetus may give signals through: • Play a role in fetal-maternal signaling for parturition
1) blood-borne agents that act on the placenta FETAL-MEMBRANE SENESCENCE
2) secretion into the amniotic fluid o Cellular senescence – physiological aging that fetal membranes undergo toward the end of pregnancy
UTERINE STRETCH o Senescent-associated secretory phenotype (SASP)
o Stretch is required for induction of specific CAPs such as: • A form of sterile inflammation manifested by the senescent fetal membrane
• Connexin-43 • Induced by stretch and oxidative stress
• Oxytocin receptors • Propagates inflammatory signals that further weaken the fetal membrane and activate signals in the
• Gastrin-releasing peptide decidua and myometrium to initiate parturition
o Mechanotransduction
• Process whereby cell signaling systems are influenced by stretch to regulate the myometrial cell
• Mechanisms: PHASE 3: LABOR
✓ Activation of cell-surface receptors or ion channels o Synonymous with active labor
✓ Transmission of signals through ECM
✓ Release of autocrine molecules acting on myometrium Stage 1 Stage 2 Stage 3
Cervical effacement & dilation Fetal expulsion Placental separation & expulsion
FETAL ENDOCRINE CASCADES
Begins: Spaced uterine Begins: Begins:
o Fetus may have the ability to provide endocrine signals that initiate parturition
contractions of sufficient frequency, Cervical dilation is complete Immediately after delivery of fetus
o Fetal hypothalamic-pituitary-adrenal-placental axis
intensity, and duration are attained
• Critical component of normal parturition
to bring about effacement Ends: Ends:
• Premature activation is considered to prompt many cases of preterm labor
Ends: Delivery Delivery of placenta
• Steroid products of fetal adrenal gland are believed to have effects that transform the myometrium to
a contractile state Cervix is fully dilated (~10 cm)
* Effacement – cervical thinning

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR
FIRST STAGE: CLINICAL ONSET OF LABOR
UTERINE LABOR CONTRACTIONS
o “Show” or “bloody show”
• Extrusion of mucus plug that had previously filled the cervical canal during pregnancy
• Indicates that labor is already in progress or likely will ensue in hours to days
o Possible causes for painful labor contractions:
• Hypoxia of the contracted myometrium
• Compression of nerve ganglia in the cervix & lower uterus by contracted interlocking muscle bundles
• Cervical stretching during dilation
• Stretching of the peritoneum overlying the fundus
o Ferguson reflex
• Mechanical stretching of the cervix enhances uterine activity CERVICAL CHANGES
• Release of oxytocin and rise in blood vessels of prostaglandin F2a may be involved o Cervical effacement
o Interval between contractions: 10 minutes (gradually narrows down towards stage 2) • “Obliteration” or “taking up” of the cervix
o Duration of contraction: 30-90 seconds, average of 1 minute • Shortening of the cervical canal from 3 cm to a mere circular orifice with almost paper-thin edges
o Amniotic fluid pressures: average 40 mm • Muscular fibers at the level of the internal os are pulled upward into the lower uterine segment
• Anatomical uterine divisions become increasingly evident • Condition of the external os remains temporarily unchanged
• Upper segment • Causes expulsion of the mucous plug
✓ Firm during contractions o Cervical dilation
Distinct lower ✓ Contracts, retracts, and expels the fetus • Canal dilates to a diameter of ~10 cm
and upper ✓ Myometrium does not relax to its original length after contractions; • Presenting fetal part descends somewhat as the cervix dilates
uterine rather, it becomes fixed as a shorter length • The lower segment and cervix have less resistance during a contraction → centrifugal pull is exerted
segments ✓ Contracts down on its diminishing contents, but myometrial tension • Hydrostatic action of the amniotic sac dilates the cervical canal like a wedge
remains constant
Latent phase Duration is more variable and sensitive to extraneous factors
✓ Becomes slightly smaller with each successive contraction and
Has little bearing on the subsequent course of labor
becomes progressively thickened
Acceleration phase Maximum slope Deceleration phase
• Lower segment
Active phase
✓ Softer, distended, more passive Characteristics of accelerated phase are predictive of labor outcome
✓ Dilate and form a greatly expanded, thinned-out tube through which the
fetus can pass
✓ Relaxation mirrors the same gradual progression
✓ Successive lengthening of the fibers accompanied by thinning
• Physiological retraction ring
✓ A ridge on the inner uterine surface, serving as a boundary between the
two segments
• Pathological retraction ring (Bandl ring)
✓ The ridge is prominent d/t extreme thinning of the lower uterine segment
• Each contraction gradually elongates the ovoid uterine shape (5-10 cm)
• Narrowing the horizontal diameter
Changes in • Effects on the labor process:
uterine shape ✓ Greater fetal axis pressure – smaller horizontal diameter straightens
the fetal vertebral column
✓ Longitudinal fibers are drawn taut – lower segment and cervix are the
only parts that are flexible and are pulled upward and around the lower
pole of the fetus
• Maternal intraabdominal pressure - serves as the most important force in fetal
Ancillary forces expulsion after the cervix is dilated fully
• Pushing – contraction of the abdominal muscles simultaneously with forced
respiratory efforts with the glottis closed o Forebag of amniotic fluid
• Leading portion of fluid and amnionic sac located in front of the presenting part
• Formed d/t effacement and dilation

~ Karrel Collantes
MD 2023
 Chapter 21: PHYSIOLOGY OF LABOR
SECOND STAGE: FETAL DESCENT Endothelins • Family of 21-amino-acid peptides that powerfully induce myometrial contraction
• Endothelin A receptor
o In many nulliparas, engagement of the head is accomplished before labor begins ✓ Preferentially expressed in smooth muscle
o Station – descent of the fetal biparietal diameter in relation to a line drawn between maternal ischial spines ✓ Activated → rise in [Ca2+]i
o Speed of descent – maximal in this stage and is maintained until the presenting part reaches the perineal floor • Endothelin-1
• In nulliparas – descent is typically slow and steady ✓ Produced in myometrium of term gestations
• In multiparas – descent may be rapid ✓ Induce synthesis of other contractile mediators
PELVIC FLOOR CHANGES Angiotensin II • Receptors are expressed in the uterus
o Most important component of the pelvic floor: levator ani + fibromuscular connective tissue covering • AT1 receptor
o Biomechanical properties change d/t altered ECM composition ✓ Expressed in gravidas
o During pregnancy – levator ani undergoes hypertrophy, forming a thick band that extends backward and ✓ Binding of Ang II = contraction
encircles the vagina about 2 cm above the plane of the hymen • AT2 receptor – in nonpregnant women
o On contraction – levator ani draws both the rectum and vagina forward and upward in the direction of the
symphysis pubis, closing the vagina
o First stage of labor – levator ani stretches + thinning of central portion of perineum PHASE 4: THE PUERPERIUM
o Anus becomes markedly dilated and presents an opening through which the anterior wall of the rectum bulges o Myometrium remains persistently contracted for about an hour after delivery
o This compresses the large uterine vessels → allows thrombosis of their lumens → prevent hemorrhage
THIRD STAGE: DELIVERY OF PLACENTA AND MEMBRANES o Uterine involution and cervical repair
o As the neonate is born, the uterus spontaneously contracts around its diminishing content • Prompt remodeling processes that restore these organs to the nonpregnant state
o The uterine fundus now lies just below the level of the umbilicus • Protect the reproductive tract from invasion by commensals
o Sudden diminution in uterine size is accompanied by a decrease in the area of the placental implantation site • Restore endometrial responsiveness to normal hormonal cyclicity
• For the placenta to accommodate itself to its reduced are, it thickens o Lactogenesis and milk let-down begin in the mammary glands
• However, d/t limited placental elasticity, it is forced to buckle o Reinstitution of ovulation signals preparation for the next pregnancy
• The resulting tension pulls the decidua spongiosa (weakest layer) from that site • Ovulation occurs within 4-6 weeks after birth
• Cleavage of the placenta is aided greatly by the loose structure of the spongy decidua • Dependent on duration of:
• As detachment proceeds, hematoma forms between the separating placenta and the adjacent decidua ✓ Breastfeeding
o The fetal membranes (amniochorion and parietal decidua) is thrown into folds → peeled off the uterine wall ✓ Lactation induced, prolactin-mediated anovulation and amenorrhea
o After the placenta has detached, it can be expelled by increased abdominal pressure
o Fundus is alternately compressed and elevated while minimal traction is exerted on the umbilical cord
Schultze mechanism Duncan mechanism
• Blood from the placental site pours into the • Placenta separates first at the periphery and
membrane sac and does not escape externally blood collects between the membranes and
until after extrusion of the placenta uterine wall and escaped from the vagina
• Placenta descends sideways; maternal
surface appears first

UTEROTONINS IN PHASE 3
• “Quick birth”; First uterotonin implicated in parturition initiation
• Nanopeptide synthesized in supraoptic and paraventricular neurons
• Neurophysin – carrier protein for prohormone
Oxytocin • Number of receptors increase appreciably = greater contractile responsiveness
• Acts on decidual tissue to promote prostaglandin release
• Maternal serum levels are elevated in:
✓ Phase 3 labor – stage 2
✓ Early puerperium
✓ breastfeeding
• Causes persistent contractions after delivery – prevent postpartum hemorrhage
Prostaglandins • Levels increased – efficient mechanism of activating contractions
• Synthesis is high and unchanging during phase 2 and 3
• Also produced by fetal membranes and placenta – PGE2, PGF2a
• Higher levels in the forebag

~ Karrel Collantes
MD 2023