[PF] Physiology of Labor Flashcards
_____ is the last few hours of human pregnancy.
Labor
It is characterized by forceful and painful uterine contractions that effect cervical dilation and cause the fetus to descend through the birth canal.
Labor
During the first _______ of normal gestation, the myometrium is in a preparatory yet unresponsive state.
36 to 38 weeks
Following this prolonged uterine quiescence, a _________ follows during which myometrial unresponsiveness is suspended and the cervix undergoes ripening, effacement, and loss of structural
cohesion.
transitional phase
The physiological processes that regulate ________ -the bringing forth of young-and the onset of labor continue to be defined.
parturition
Three general contemporaneous theories describe labor initiation.
- functional loss of pregnancy maintenance factors
- synthesis of factors that induce parturition
- signal or parturition commencement (mature fetus is the source of the initial)
________ remains the major contributor to neonatal mortality and morbidity.
Preterm labor
The __________ of the uterus is composed of bundles of smooth muscle cells surrounded by connective tissue.
myometrial layer
In contrast to skeletal or cardiac muscle, the __________ is not terminally differentiated and therefore is readily adaptable to environmental changes
smooth muscle cell
Lining the thick muscular uterine walls, the endometrium is transformed by pregnancy hormones and is then termed _________
decidua
Composed of stromal cells and maternal immune cells,
the _______ serves to maintain the pregnancy via unique immunoregulatory functions that suppress inflammatory signals during gestation.
decidua
Maintenance of barrier function to protect the
reproductive tract from infection
Cervix
maintenance of cervical competence despite greater gravitational forces as the fetus grows
Cervix
orchestration of extracellular matrix changes that allow progressively greater tissue compliance
Cervix
In nonpregnant women, the cervix is ______ and ______ and its consistency is similar to nasal cartilage.
closed and firm
By the end of pregnancy, the cervix is easily _________, and its consistency is similar to the lips of the oral cavity
distensible
Concurrent with expansion of the stroma, the ____________ proliferate and exert a pregnancy-specific immunoprotection.
cervical epithelia
In addition to providing the exchange of nutrients and waste between mother and fetus, the _________ is a key source of steroid hormones, growth factors, and other mediators that maintain pregnancy and potentially aid the transition to parturition.
placenta
The fetal membranes ______, _______ and _______ make up an important tissue shell around the fetus that serves as a physiological, immunological, and metabolic shield to protect against untimely parturition initiation.
amnion
chorion
adjacent decidua
The _______ provides virtually all of the fetal membranes’ tensile strength to resist membrane tearing and rupture.
amnion
This avascular tissue is highly resistant to penetration
by leukocytes, microorganisms, and neoplastic cells.
amnion
It also constitutes a selective filter to prevent fetal particulate-bound lung and skin secretions from reaching the maternal compartment.
amnion
The ______ is a primarily protective tissue layer and provides immunological acceptance. It is also enriched with enzymes that inactivate _______, which are agents that stimulate contractions.
chorion
uterotonins
Inactivating enzymes include:
Prostaglandin dehydrogenase
Oxytocinase
Enkephalinase
In many species, the role of sex steroid hormones is clear- _________ promotes and __________ inhibits the events leading to parturition.
estrogen
progesterone
The removal of progesterone, that is ______________ directly precedes progression of parturition
progesterone withdrawal
In addition, providing progesterone to some species will delay parturition via a decline in _____________ and continued _________.
myometrial activity
cervical competency
In all species studied including humans, administration of the progesterone-receptor antagonists ________ or _______ will promote some or all key features of parturition. These include cervical ripening, greater cervical distensibility, and augmented uterine sensitivity to uterotonins.
mifepristone (RU-48) or onapristone
Estrogen can advance progesterone responsiveness
and in doing so promote _____________.
uterine quiescence
At the end of pregnancy, __________ aids processes that mediate uterine activation and cervical ripening.
estrogen
Two nuclear receptors for estrogen are:
estrogen receptor a (ERa)
estrogen receptor 3 (ER3)
Nuclear receptor isoforms of the progesterone receptor _______ and ______ are encoded by differing transcripts from a single gene.
(PR-A and PR-B)
_________ are lipid molecules with varied hormone-like actions.
Prostaglandins
In parturition, they play a prominent role in myometrial contractility, relaxation, and inflammation.
Prostaglandins
Prostaglandins interact with a family of ____ different G-protein-coupled receptors several of which are expressed in myometrium and cervix.
eight
Prostaglandins are produced using plasma membrane-derived _________, which usually is released by the action of ___________.
arachidonic acid
phospholipase A2 or C
Arachidonic acid can then act as substrate for both type 1 and 2 prostaglandin H synthase (PGHS-l and -2), which are also called ___________.
cyclooxygenase -l and -2 (COX-l and -2)
Both PGHS isoforms convert arachidonic acid to the unstable ________ and then to prostaglandin H2. These enzymes are the target of many ______.
prostaglandin G2
nonsteroidal anti-inflammatory drugs (NSAIDs)
Through prostaglandin isomerases, __________ is converted to active prostaglandins. These include prostaglandins E2 (PGEJ, F2x (PGF2x), and 12 (PGI2
).
prostaglandin H2
Another important control point for prostaglandin activity is its metabolism, which most often is through the action of _____________.
15-hydroxyprostaglandin dehydrogenase
PGDH
Expression of this enzyme is up regulated during pregnancy in the uterus and cervix, which provides the important ability to rapidly inactivate prostaglandins.
15-hydroxyprostaglandin dehydrogenase
PGDH
It is entirely possible that __________ contribute to myometrial relaxation at one stage of pregnancy and to myometrial contractions after parturition initiation.
prostanoids
The _______ is likely the major source for amnionic fluid prostaglandins, and their role in the activation of cascades that promote membrane rupture is clear.
amnion
PHASE 1:
UTERINE QUIESCENCE AND CERVICAL SOFTENING
Parturition can be arbitrarily divided into four overlapping phases that correspond to the major
physiological transitions of the myometrium and cervix during pregnancy. These phases of parturition include:
(1) a prelude to it
(2) the preparation for it
(3) the process itself
(4) recovery
Importantly, the phases of parturition should not be confused with the ____________, that is, the first, second, and third stages-which make up phase 3 of parturition.
clinical stages of labor
The myometrial cells undergo a phenotypic modification to a noncontractile state, and uterine muscle is rendered unresponsive to natural stimuli.
Phase 1
That said, some low-intensity myometrial contractions are felt during the quiescent phase but they do not normally cause cervical dilation. These contractions
are common toward the end of pregnancy, especially in multiparas, and are referred to as ________.
Braxton Hicks contractions or false labor.
The quiescence of phase 1 likely stems from:
(1) actions of estrogen and progesterone via intracellular receptors
(2) myometrial-cell plasma membrane receptor-mediated increases in cyclic adenosine monophosphate (cMIP)
(3) generation of cyclic guanosine monophosphate (cGMP)
(4) other systems, including modification of myometrial-cell ion channels.
diminished intracellular crosstalk and reduced intracellular Ca2+ ([Ca2 +)] levels
Quiescence
ion channel regulation of cell membrane potential
Quiescence
enhanced interactions between the actin and myosin proteins
Contractility
heightened excitability of individual myometrial cells
Contractility
activation of the uterine endoplasmic reticulum stress-unfolded protein response
Quiescence
promotion of intracellular crosstalk that allows synchronous contractions to develop
Contractility
uterotonin degradation
Quiescence
Indeed, a potential mechanism for maintenance of
_______ is the promotion of actin into a globular form rather than into fibrils, which are required for _______.
relaxation
contraction
Moreover, ______ must be attached to the cytoskeleton at focal points in the cell membrane to allow tension to develop.
actin
The coupling of myosin and actin activates ____________, hydrolyzes adenosine triphosphate, and generates force.
adenosine triphosphatase (ATPase)
This interaction is brought about by ___________ of the 20-kDa light chain of myosin
enzymatic phosphorylation
This is catalyzed by the enzyme __________, which is activated by calcium.
myosin light-chain kinase
Calcium binds to _______, a calcium-binding regulatory protein, which in turn binds to and activates myosin light-chain kinase.
calmodulin
Thus, logically, uterine relaxation ordinarily is promoted by conditions that _______ concentrations of (Ca2+)i.
lower
But, contractions can be prolonged by inhibition of ___________, an enzyme which dephosphorylates myosin.
myosin phosphatase
In normal physiology, the myometrial ________ plays dual and opposing roles to maintain a balance between uterine quiescence and contractility.
BKca channel
The Bca channel is abundantly expressed in the _________.
myometrium
Enhancing Bca channel opening results in myometrial ________ whereas inhibition of the Bca channel augments myometrial _________.
relaxation
contractility
Communication is established between myocytes by ________ which aid the passage of electrical or ionic coupling currents as well as metabolite coupling.
gap junctions
The transmembrane channels that make up the gap
junctions consist of two protein ___________.
“hemi-channels”
These ________ are each composed of six connexin subunit proteins.
connexons
___________ is expressed in myometrium, and concentrations rise near labor onset.
Connexin-43
Optimal numbers and types of gap junctions are believed to be important for electrical ___________.
myometrial synchrony
_________ maintains uterine quiescence in part by mechanisms that lower expression of various key proteins needed for contractility.
Progesterone
These ___________ include the oxytocin receptor, prostaglandin F receptor, and connexin-43.
contraction-associated proteins (CAPs)
As another potential mechanism, progesterone maintains uterine quiescence through support of myometrial ______ which is an anticontractile agent
caspase 3
This protein degrades both actin and the specific gap junction protein, connexin-4.
caspase 3
In mice, myometrial caspase 3 activation is regulated by a pregnancy-induced _______________. Prolonged ERSR promotes caspase 3
activation to preserve quiescence despite these stimuli.
endoplasmic reticulum stress response (ERSR)
As background, the __________ aids protein folding and transport.
endoplasmic reticulum
_____________ cause misfolded proteins to accumulate and trigger the ERSR.
Functional irregularities
The ERSR and its ______________ are cellular mechanisms that work to maintain homeostasis in the face of stimuli, such as stretch and inflammation.
unfolded-protein response (UPR)
Prolonged ERSR promotes _________ to preserve quiescence despite these stimuli.
caspase 3 activation
___________ are prototypical examples of cAMP signaling causing myometrium relaxation.
B-Adrenoreceptors
Levels of myometrial _____ receptors during pregnancy are greater before than during labor.
LH-hCG
_________ acts to activate adenylyl cyclase by way of a plasma membrane receptor
G’s-linked system.
Chorionic gonadotropin
Thus, high circulating levels of hCG may be one mechanism of ________.
uterine quiescence
_________ mediates its diverse cellular effects through four G-protein-coupled receptors.
Prostaglandin E2
Specifically, __________ are expressed in the myometrium during pregnancy and with labor onset.
prostaglandin E receptors 1 through 4 (EP1,-EP 4)
___________ act through G’s to raise cAMP levels and maintain myometrial cell quiescence but switch to a G’alpha/ 1 1 calcium-activating pathway during labor.
EP2 and EP4
_______ receptors act through G’alpha q and G’alpha i to augment intracellular Ca2+ and contractility.
EP1 and EP3
The peptide hormone _______ binds to the G-protein coupled receptor named relaxin famiy peptide receptor 1 (FP 1).
relaxin
