Physiology, Pregnancy Contractions


Article Author:
Austin McEvoy


Article Editor:
Maggie Tetrokalashvili


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Tehmina Warsi


Updated:
12/6/2018 6:30:12 PM

Introduction

It is important for clinicians to understand the normal physiology of uterine contractions so they can better identify abnormalities that may lead to obstetrical complications, including preterm labor and arrest of labor. Knowing the cellular mechanism of uterine contractions also allows clinicians to better understand pharmacotherapy used for labor augmentation, induction, and tocolysis. Uterine contractions also play an important role in minimizing postpartum bleeding, which explains why many drugs used to treat this complication target pathways involved in myometrial contractility.

Cellular

The uterus has 3 layers: endometrium, myometrium, and an outer serosal layer. The muscular layer, also known as the myometrium, is located between the endometrium and the serosal layer. The myometrium itself has 2 layers: a circular muscle layer and a longitudinal muscle layer.[1] These layers work together to expel the fetus from the uterine cavity. Some studies have suggested that myometrial cells exhibit "pace-maker" capabilities that facilitate synchronous uterine contractions, although the evidence for this is inconsistent.[2]

There are several receptors on the surface of myometrial cells that affect contractility. These include:

  • Oxytocin receptors: Contractility agonist
  • Estrogen receptors: Contractility agonist 
  • Progesterone receptors: Contractility antagonist 
  • Beta2 adrenergic receptors: Contractility antagonist 

These receptors are the targets of many drugs used in the management of abnormal labor. 

Organ Systems Involved

Myometrial contractions primarily involve the uterus itself and well as the endocrine system. The process starts with the hypothalamus, specifically the paraventricular and supraoptic nuclei. These nuclei generate and secrete oxytocin, the major contributor being the paraventricular nucleus. Oxytocin then travels to the posterior pituitary via the hypothalamic-hypophysial tract. After oxytocin arrives in the posterior pituitary, it then access the systemic blood supply which delivers the oxytocin molecule to oxytocin receptors on myometrial cells. The uterine epithelial lining also makes oxytocin during pregnancy, the amnion, and placenta where it acts in both autocrine and paracrine fashion.[3][4] The positive feedback mechanism of oxytocin further catalyzes the onset of labor.[5][6][7]

Function

The primary function of uterine contractions is to expel the fetus from the uterine cavity. However, contractions also play an important role in minimizing postpartum bleeding.

Mechanism

The exact sequence of events that leads to uterine contractions is still largely unknown. Some studies suggest mechanical stretch and hormones work together to initiate contractions in normal labor.[2] However, due to the role of inflammation in preterm labor, other studies suggest that inflammatory mediators, such as cytokines and prostaglandins, initiate uterine contractions.[8] 

Mechanical Stretch

Mechanical stretch refers to tension on myometrial cells as the uterus distends. The physical stretching of the uterus causes an influx of ions, namely sodium and calcium, that changes the action potential across myometrial cells.[9][10] This facilitates the onset of uterine contractions. The number of connexins (gap junctions) between myometrial cells increases just before labor, which allows coordinated muscle contraction. These cell-to-cell contacts are less abundant early in pregnancy, favoring uterine quiescence.[11] It has also been suggested that uterine overdistention causes an "inflammatory pulse" that further activates myometrial contractility.[12]

Inflammatory mediators

Many studies suggest labor is mediated by inflammation.[12][13] Inflammatory markers most notably include prostaglandins, which increase in concentration before the onset of labor due to a functional progesterone withdrawal, leading to an increased estrogen to progesterone ratio.[14]

The two most studied prostaglandins involved in uterine contractions include prostaglandin E1 (PGE1) and prostaglandin E2 (PGE2.) Misoprostol is the synthetic version of PGE1, which although originally designed to prevent peptic ulcers, proved to have a dose-dependent effect on myometrial contractility.[14]

PGE2 also plays a role in uterine contractions by activating EP1 and EP3 receptors on myometrial cells.[15] The major physiological effect of PGE2 during labor, however, is activation of inflammatory mediators Il-8 and TNF-alpha that activate of collagenases and MMPs, leading to the ripening of the cervix.[14]

Prostaglandin F2 alpha (PGF2a) in less studied, but it is thought to both decrease progesterone levels and independently increases uterine contractility by stimulating smooth muscle cells.[16]

Prostaglandins also play a role in uterine contractions after the delivery of the fetus. During this time, also known as stage 3 of labor, the placenta secretes prostaglandins that lead to its detachment from the endometrial cavity.[17] Contractions during this period also minimize postpartum bleeding. Lack of contractions during this period can occur due to uterine atony.

Hormones

The primary hormones involved include estrogen, progesterone, and oxytocin. Oxytocin is one of the most widely studied hormones involved in uterine contractions. Studies suggest that the increased estrogen to progesterone ratio that occurs before the onset of labor leads to an increased number of oxytocin receptors on the uterus.[18] Many animal studies also show an increase in oxytocin concentration before labor; however, there is limited evidence regarding this phenomenon in humans due to technical difficulties in obtaining oxytocin levels in laboring women.[5]

During labor, oxytocin is released from the posterior pituitary and exhibits positive feedback upon activation of receptors on myometrial cells. These receptors are rhodopsin class 1 G proteins that are coupled to phospholipase C (PLC), which then activates inositol triphosphate (IP3) and diacylglycerol (DAG.) Activated IP3 mobilizes calcium from the sarcoplasmic reticulum which then binds to myosin light chain kinases resulting in smooth muscle contraction.[5]

It has also been suggested that calcium released from the sarcoplasmic reticulum within myometrial cells activates L-type calcium channels (voltage-gated) on the surface of the myometrial cell membrane, allowing a further influx of calcium ions that exert a positive inotropic effect on myometrial contractility.[5]

Related Testing

The primary clinical methods of monitoring myometrial activity include the use of external tocometers and intrauterine pressure catheters. Although both devices allow visualization of contractions in relation to the fetal heart rate, only intrauterine pressure catheters allow precise measurement of the strength of uterine contractions.

External Tocometer

Two probes are placed on the woman’s abdomen, one over the uterine fundus, the other in proximity to the fetal heart. This is the standard method of monitoring uterine contractions in laboring women. 

Intrauterine Pressure Catheter

A thin catheter is inserted into the uterus and monitors changes in pressure. The standard unit of measurement is the Montevideo unit (MVU). Adequate contractions are defined as a total 200 MVU within 10 minutes. Internal monitoring has limited use because it requires rupture of fetal membranes for placement. It is commonly used in combination with a fetal scalp electrode that monitors fetal heart rate.

Clinical Significance

Understanding the physiology of uterine contractions allows clinicians to use targeted therapy for both the induction and cessation of labor. Commonly used medications for induction of labor include oxytocin, misoprostol, and dinoprostone.  Because uterine contractions dually function to minimize postpartum bleeding, these are the same medications used to manage postpartum hemorrhage. Carboprost, an analogue of PGF2a, is an additional medication used to manage postpartum hemorrhage that is not used for induction of labor.

Medications used to stop preterm labor antagonize uterine contractions. Commonly used tocolytics include nifedipine, terbutaline, magnesium sulfate, indomethacin, and atosiban. Of these tocolytic agents, beta sympathomimetics, oxytocin receptor antagonists, and calcium channel blockers have the most promising data in terms of efficacy.[19] Figure 1 summarizes the medications used for induction of labor and tocolysis.

Knowing the normal physiology of uterine contractions also allows clinicians to better differentiate between the true onset of labor and prodromal labor, also known as Braxton Hicks contractions. True labor consists of contractions at regular intervals. As labor progresses, these contractions become stronger and the time between each contraction decreases. The contractions of prodromal labor occur sporadically and do not increase in strength.

Understanding the normal pattern of contractions is also useful in defining the arrest of labor, which has different management based on the stage. For example, an arrested latent phase is an indication for augmentation with oxytocin, while an arrested active phase is an indication for cesarean section. Defining true arrest of labor requires analysis of the adequacy of uterine contractions, which requires the use of an intrauterine pressure catheter. Active phase arrest has specific requirements, which includes 4 or more hours of adequate contractions, or 6 or more hours of inadequate contractions. These definitions are important for clinicians because they dictate management algorithms.


  • Image 7028 Not availableImage 7028 Not available
    Contributed by Austin McEvoy, MS4
Attributed To: Contributed by Austin McEvoy, MS4

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Physiology, Pregnancy Contractions - Questions

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A 29-year-old wheelchair-bound female with a history of a complete L4 spinal cord section presents to her gynecologist complaining of amenorrhea. Her last menstrual period was 12 weeks ago. The patient says she took an at-home pregnancy test and that it was positive. Beta-HCG in the office is 100,000. Ultrasound confirms intrauterine pregnancy. Which of the following is the most appropriate management of this patient?



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A 17-year-old G1P0 arrives to the emergency department complaining of intermittent abdominal pain and leakage of clear, vaginal fluid. Her gestational age is 38 weeks based on her first-trimester ultrasound. She is admitted to the labor and delivery service and is monitored with an external tocometer that shows the patient is actively contracting. Before this patient’s arrival to the ED, which of the following molecular changes most directly caused an increase in prostaglandin concentration?



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Active phase arrest is defined as cervical dilation of 6 cm or greater with ruptured membranes and no cervical change with how many hours of adequate contractions?



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A 32-year-old G4P3 at 33 weeks gestation presents to the emergency department complaining of intermittent abdominal pain she says feels like contractions. She also reports fever, chills, and dysuria of 3 days duration. She denies vaginal bleeding and any leakage of fluid. On physical exam, she has mild costovertebral angle tenderness on the right. Urine specimen obtained via catheterization yields a colony count of greater than 100 CFU/mL. White blood cell casts are also identified. The patient is started on intravenous ceftriaxone and is admitted to the labor and delivery service. Which of the following medications would most effectively prevent preterm labor in this patient?



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Which of the following structures does not secrete oxytocin?



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A 32-year-old G3P2 at 35 weeks gestational age presents to obstetric triage complaining of contractions that began 8 hours ago. She reports that the pain is worsening and that her contractions are now occurring every 3 to 4 minutes. She endorses good fetal movement. She denies rupture of membranes, vaginal bleeding, or dysuria. She is admitted to labor and delivery for preterm labor. Which of the following cellular level changes occurs just before labor that allows synchronous myometrial contractions?



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Physiology, Pregnancy Contractions - References

References

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