Physiology of Parturition

Question 1

Hormonal mechanisms to maintain myometrial queiscence during pregnancy

Answer 1

• Myometrial inhibitor is progesterone, a smooth muscle relaxant, pro-gestation hormone. Blocks MLCK and thus the action of prostaglandins, promoting quiescence.
• Progestin uses NO → cGMP to inhibit myosin, actin, and calcium interaction.
• CRH interacts through cAMP and PKA to inhibit these interactions, and stimulates NO as well.

Question 2

Types of proteins that contribute to myometrial contractility

Answer 2

• proteins that promote contractility of actin and myosin
• proteins that increase myocyte excitability
• proteins that promote intracell connectivity

Question 3

Characteristics of proteins that promote contractility of actin and myosin

Answer 3

• Calmodulin and increased calcium → activate myosin light chain kinase (MLCK) → MLCK activates myosin via phosphorylation.
• Following myocyte depolarization there is an influx of [Ca2+]E through voltage-regulated calcium channels and the release of calcium from intracellular stores results in an increased [Ca2+]I, thereby promoting myosin-actin interactions and, consequently, contractions

Question 4

Characteristics of proteins that increase myocyte excitability

Answer 4

• ↓ Na+/K+ exchange pumps → At the time of labor, the function and distribution of these channels are altered so that a lower intensity stimulus is required to depolarize myocytes and produce the associated influx of calcium that generates contraction
• ↓ β2 and β3 - sympathomimetic receptors. These normally ↑ the opening of potassium channels, which reduces the excitability of the cell

Question 5

Characteristics of proteins that promote intracell connectivity

Answer 5

• As parturition progresses → ↑synchronization of the electrical activity of the uterus
• This is achieved via connecting myofibrils and through the production of prostaglandins, which act in a paracrine fashion to depolarize neighboring myocytes → increased recruitment into contraction
• Multimers of connexin 43 connect myocytes, permitting function in concert

Question 6

Phases of myometrial activation

Answer 6

0 - Quiescence

1 - Activation → it is unclear what signals the switch from quiescence to activation

2 - Stimulation → encompasses labor phases 1 - 3 (next LO)

3 - Involution → corresponds to phase 4 of labor; the six hours post delivery

Question 7

Define: 4 clinical stages of labor

Answer 7

1. Onset of effective contractions to complete dilation of the cervix
   
   1. Latent phase → Cervix closed
   2. Active phase → Cervix thinned out
2. Complete dilation of the cervix to delivery of the fetus
3. Delivery of the fetus to delivery of the placenta
4. First 6 hours after delivery. After this, mom is usually by this time in the clear, ↓ risk of complication

Question 8

Mechanisms of increased calcium near term

Answer 8

• Put simply, prostaglandins (PGE) and oxytocin (OT) binding stimulate ligand-gated calcium receptors.
• PGE and OT also promote Ca2+ release from SR
• All of this intracellular Ca2+ triggers the opening of voltage gated Ca2+ channels and depolarization of the cell.
• And then….
  
  • Calcium enters the depolarizing cell and combines with calmodulin to form calmodulin–calcium complexes that activate myosin light-chain kinase, which in turn phosphorylates the myosin light chain.
  • ==> generation of ATPase activity ==> sliding of myosin over the actin filaments = contraction

Question 9

Role of CRH and cortisol in initiation of parturition

Answer 9

• CRH
  
  • Stimulates labor
  • Induces fetal cortisol secretion which → fetal pulmonary maturity,
  • ↑ rapidly before delivery and peaks at delivery
• Fetal cortisol induces fetal pulmonary maturity

Question 10

Role of estrogens in initiation of parturition

Answer 10

• Induce contraction.
• Increases in inflammatory factors such as COX-2 and IL-8 which are early events in the progression to active labor.
• These increases precede changes in progesterone receptors, which cause changes in estrogen receptors and, as a consequence, expression of connexin 43 and the oxytocin receptor

Question 11

Role of oxytocin and PGs in initiation of parturition

Answer 11

• Oxytocin
  
  • Stimulates contractions
  • Activates MLCK,
  • ↑ intracellular Ca2+
  • Activates prostaglandins
• Prostaglandins
  
  • Stimulate myometrial contractions
  • ↑ intracellular Ca2+

Question 12

Role of fetal hypothalamic-pituitary axis in parturition

Answer 12

• As term approaches, there is an ↑corticotropin by the fetal pituitary and ↑steriodogensis in the fetal adrenal glands.
• ↑ fetal cortisol → maturation of fetal lungs → maturing fetal lungs ↑ surfactant production.
• Amniotic fluid surfactant proteins stimulate the inflammation that is observed in the adjacent fetal membranes, cervix and underlying myometrium at the time of labor.
• This inflammatory process is one element that leads to the onset of labor.

Question 13

Maternal conditions assoc. w/preterm birth

Answer 13

• Chronic HTN / HTN disorders of pregnancy
• SLE
• Restrictive lung disease
• Hyperthyroidism
• Pre-gestational DM
• GDM
• Maternal cardiac disease
• Asthma
• Pre-gestational renal disorders

Question 14

Fetal/infant conditions assoc. w/preterm birth

Answer 14

• Cerebral palsy: Swedish study → 50% of children with cerebral palsy had been born prematurely
• Hypothermia
• Hypoglycemia
• RDS
• Neonatal jaundice
• Respiratory illnesses
• Necrotosing enteritis
• Intraventricular brain hemorrhage
• Hearing impairments, retinopathy of prematurity
• Higher incidence of motor impairment, ADHD