Parturition Flashcards
1
Q
4 clinical stages of labor
A
- Effective contractions to complete dilation of the cervix
- Complete dilation (10cm) to delivery of the fetus
- Delivery of the fetus to delivery of the placenta (30 min)
- First 6 hours after delivery
2
Q
myometrial activation (phase 1)
A
1
3
Q
Mechanism of myometrial quiescence (phase 0)
A
1
4
Q
Progesterone in quiescence and parturition
A
Myometrial inhibitors:
Quiescence mid- trimester
Reduced activity MAY contribute to labor last trimester
- progesterone withdrawal activates mitogen-associated protein kinase and increases contractility
5
Q
CRH in quiescence and parturition
A
Myometrial inhibitors:
- maintains quiescence mid trimester
Myometrial stimulants:
- Signal for parturition, last trimester
- Change in receptors
6
Q
Cortisol in quiescence and parturition
A
1
7
Q
Oxytocin in quiescence and parturition
A
Myometrial stimulants
- Stimulates contractions
- Differential distribution on uterus, highest at fundus
8
Q
Contraction activated proteins (CAPS) and their contribution to contractility
A
CAPS protein synthesis
- Gap jxns
- Calcium channels
- Oxytocin receptors
- Prostaglandin receptors
- act within the uterus, to initiate powerful rhythmic contractions
Three types of CAPs:
- Those that enhance the intxns betwn actin + myosin –> muscle contraction
- Those that increase excitability of myometrial cells
- Those that promote the intercellular connectivity that permits the development of synchronous contractions
9
Q
How do myometrial calcium increases near term
A
1
10
Q
Role of fetal HPA axis in partuition
A
1
11
Q
Labor
A
effective uterine contractions leading to dilation and effacement of the cervix and delivery of the fetus
12
Q
In between contraction
During contraction
A
blood flow in and blood flow out is good
Blood flow in and out is stopped
13
Q
Carries deoxygenated blood
A
umbilical arteries
14
Q
5 fxns of cervix
A
- Baby in
- Baby out
- Endometrium out
- Sperm in
- Bugs out (keep infxns from ascending)
15
Q
Structure of cervix
A
- Stroma is collagen I & II
- Collagen has linked strands
- Proteases degrade collagen
- Edema in later pregnancy
- Dilates passively with contractions
16
Q
Power
Myometrial expulsive efforts
+
Maternal expulsive efforts
A
Phase 0 - Quiescence
Phase 1 - Activation
Phase 2 - Stimulation
Phase 3 - Involution
Maternal expulsive efforts
- Push push push!
17
Q
Myometrial phase 2
A
Stimulation involves: 1. Contraction to dilation 2. Dilation to baby 3. Baby to Placenta
18
Q
Myometrial phase 3
A
6 hours post partum
19
Q
Uterus changes during pregnancy
A
- 50g –> 1000g
- Growth primarily cellular hypertrophy
- Increased connectivity
- Increased oxytocin receptors 100-200x
- Receptors most highly [ ] in fundus
20
Q
Synchronicity theory
- Action potential propagation in regions
A
- EMG’s of the abdomen in labor
- Estimated 20-30 of these
- Myofibril Cells connected by gap jxns
- Think Goldberg polyhedron *soccer
Mechano-transduction across the uterus
- one region contract –> P rises
- Triggers stretch initiated contractions elsewhere
- Synchrony is achieved by electrical conduction through connecting myofibrils –> transmits electrical activity to nearby muscle fibers –> activated myocytes produce prostaglandins –> act in paracrine fashion to depolarize neighboring myocytes
21
Q
Prostaglandins
A
fxn: stimulates contraction
Mechanisms:
- Act in a paracrine fashion
- Increase intracellular calcium levels
- Facilitates weakening of amnion and chorion
22
Q
CRH
*see slide
A
fxn:
Early pregnancy - Quiescence
Late pregnancy - Contraction (stim labor)
Mechanisms:
- Early pregnancy - blocks myosin light chain kinase
- Late pregnancy - Protein kinase C pathway
Positive feedback system on maternal side
Pulmonary maturation on fetal side
23
Q
Term labor weeks
A
37-42 weeks
24
Q
How does CRH help with fetal pulmonary maturity?
A
CRH stimulates labor
CRH induce fetal pulmonary maturity
- less morbidity with labor than with C section
- absence of above
25
Oxytocin
Fxn
Mech
Fxn: stimulates contraction
Mechanisms:
1. Binds membrane receptors
2. Increases intracellular calcium levels
3. Activates myosin light chain kinase
4. Activate prostaglanding E & F2 alpha production
5. Increases intracellular calcium lvls
6. activates myosin light chain kinase
26
Progesterone at term
- Blocks myosin light chain kinase
- Inactivates prostaglandins
1. Progesterone lvls high
2. reduced receptor number
3. different receptor types
4. less progesterone activity
27
Preterm birth occurs in how many pregnancies?
5-15%
* rising in developed countries
- esp in black Americans
- birth b4 37 weeks of gestation assoc. w/ 70% of neonatal deaths
*black women have lower maternal CRH [ ] than others that correlate with timing of birth
28
The timing of birth is associated with the development of what?
maternal CRH - which is made by the placenta (syncytiotrophoblast)
29
Diff between release of maternal plasma CRH lvls at term and preterm, and after term.
term: CRH lvls increase exponentially
preterm: CRH exponential increase is super rapid
After term: rise is slower
30
What stimulates expression of the CRH gene and production of CRH by the placenta?
Glucocorticoids
GC --> CRH --> stim pituitary to produce corticotropin --> stim adrenal cortex to produce cortisol + DHEAS
31
Are all cases of preterm birth related to changes in CRH production?
No - uterine infxn is a common cause
*but a high CRH lvl has a relatively specific associattion with greatly increased risk of preterm birth
32
CRH receptors change to what G protein signaling at term?
Prior to term:
G protein --> relax myometrial cells
Term:
CRH receptors change to Gq --> PKC activation -->
contractile pathways
33
CRH receptors in mom = _______
CRH receptors in fetus =
_______
CRH receptors in mom = pituitary, myometrium, adrenal glands
CRH receptors in fetus =
pituitary, adrenal glands, lungs
* CRH stimulates fetal lung developmenet and induce surfactant phospholipid synthesis
* CRH also stim adrenal prod of DHEAS --> E2 --> favor parturition by inducing contraction
34
How does the syncytiotrophoblast release of CRH result in fetal lung development?
Syncytiotrophoblast CRH -->
maternal blood --> adrenal cortex makes cortisol -->
Maternal artery into intervillous space -->
stim more CRH prod by syncytiotrophoblast -->
stim fetal pituitary to synth corticotropin-->
drive fetal adrenal cortisol and DHEAS synthesis -->
Stim fetal lungs to produce surfactant protein A (moves amniotic fluid to the amnion, where it stimulates the production of COX-2 and PGE)
35
When is myosin (actin's partner) activated and promote myosin-actin intxn and ultimately, contraction?
when myosin is phosphorylated by myosin light chain kinase (MLCK)
*Calmodulin and and increased intracellular Ca2+ activate this enzyme
36
How does labor affect Na/K pumps?
Labor lowers the intensity of the stimulus required to depolarize myocytes and
produces the influx of Ca2+ that generates contraction.
- reduces the excitability of the cell at labor
37
How is blood flow to the fetus affected by: periods of relaxation
+ periods of contraction
periods of relaxation: permit blood flow to the fetus
periods of contraction:
blood flow to fetus decreases
*uterus lacks pacemaker that regulates contractions
38
Describe how synchrony is achieved through myometrium conversion during labor
During labor, uterine myometrium is converted from tissue w/ low connectivity into tissue with extensive connxns via pores formed by multimers of connexin 43.
Synchrony is achieved by electrical conduction through connecting myofibrils --> transmits electrical activity to nearby muscle fibers --> activated myocytes produce prostaglandins --> act in paracrine fashion to depolarize neighboring myocytes
39
At the time of labor, depolarization occurs when ____ and _____ bind to cell surface receptors, thereby promoting opening of ligand regulated CCs.
PGF2a
Oxytocin
40
Before labor, how is the relaxed state of the uterus maintained?
1. Range of factors increase intracellular cAMP -->
activate PKA --> promote phosphodiesterase activity and dephosphorylation of MLCK
2. Actin is maintained in globular form (not fibrillar) and is unable to contract
* at labor, this is reversed
- Calmodulin- Ca2+ complexes activate MLCK and phosphoylates MLC --> generase ATPase and promotes sliding of myosin over actin filaments --> contraction
41
What facilitates placental membrane rupture?
Prostaglandins + CRH: they mediate release of metalloproteases that weaken the placental membrane (degrade collagen)
42
Cortisol and sufactance proteins activate inflammatory pathways in the amnion, leading to ________ and _____ activation
cervical softening and myometrial activation
*figure 5 in reading is good
43
Myometrial activation in pregnancy involves progesterone withdrawal and increased production of COX-2, which _______ and _____
synthesizes prostaglandins and promotes contraction
44
Inflammatory factors that lead to the progression of labor
Cox-2 and IL-8
*note that infxn also activates inflammation and may stimulate PG synth in fetal membranes.
45
Abruption appears to affect the _____ directly through the release of ____, a potent stimulator of myometrial contraction.
Myometrium
Thrombin
