Parturition And Lactation

Question 1

When does human birth usually occur?

Answer 1

At 40 weeks of gestation (38 weeks fetal age)

Question 2

What does parturition involve?

Answer 2

Transformation of the myometrium from quiescent to highly contractile
Remodeling of the uterine cervix such that it softens and dilates
Rupture of the fetal membranes
Expulsion of the uterine contents
Return of the uterus to its pre-pregnant stage

Question 3

Describe the changes in uterine activity that occur during pregnancy

Answer 3

Most of pregnancy uterus is relaxed and insensitive to hormones that stimulate contractions (prostaglandins and oxytocin)
Uterus grows and distends to accommodate developing fetus, placenta, amniotic fluid
Uterine myometrial cells undergo significant hypertrophy

Question 4

What are Braxton Hicks contractions?

Answer 4

Weak irregular contractions that occur towards the end of pregnancy
Not powerful enough to induce labor
Thought to prepare the uterus for parturition

Question 5

What are the two major categories of effects that lead up to the intense contractions of parturition?

Answer 5

Progressive hormone changes

Progressive mechanical changes

Question 6

Which hormones are invovled in the hormonal changes that lead up to the intestine contractions of childbirth?

Answer 6

Progesterone, estrogens, prostaglandins, oxytocin, relaxin

Question 7

Reciprocal changes in which uterine hormone receptors are necessary for onset of labor?

Answer 7

Progesterone and estrogens

Question 8

What are the effects of progesterone?

Answer 8

Promotes myometrial relaxation during pregnancy
Blocks contractions of labor
Treatment with nuclear progesterone antagonists increases myometrial contractility/excitability (can induce labor at any stage of pregnancy)
Thought to be a desensitization of uterine cells to actions of progesterone
-functional rather than systemic withdrawal
-leads to an increase in estrogen receptor expression

Question 9

What are the effects of estrogen?

Answer 9

Following progesterone desensitization there is an increase in estrogen receptor expression
Increase myometrial contractility and cervical dilation
Oppose actions of progesterone by increasing responsivenesss to oxytocin and prostaglandins
-stimulate formation of gap junctions
-increase numbers of oxytocin receptors in myometrium decidual tissue
Increase production/release of prostaglandins by fetal membranes
Stimulation expression of proteolytic enzymes in cervix (e.g. collagenase)

Question 10

What are the effects of prostaglandins?

Answer 10

Stimulate strong myometrial contractions
Will initiate labor (large doses of PGF2a and PGE2 can induce myometrial contractions at any stage of gestation)
PGF2a potentiates oxytocin induced contractions by promoting formation of gap junctions which allows for synchronous contraction
Stimulates effacement (thinning) of cervix early in labor

Question 11

What stimulates synthesis of prostaglandins?

Answer 11

Estrogen in fetal membranes, oxytocin in uterine cells, uterine stretch

Question 12

What are the effects of oxytocin?

Answer 12

Uterus is insensitive to oxytocin until ~20 weeks
Estrogen increases the oxytocin receptors
80x higher than baseline by ~36 weeks and 200x by early labor
Uterine myometrium for smooth muscle contraction
Stimulates PGF2a production on decidual tissue

Question 13

What hormonal changes occur during active labor?

Answer 13

Oxytocin stimulates uterine contractions that sustain labor
Stimulates PGF2a production in decidual cells
Released in bursts during active labor (frequency increases as labor progresses)

Question 14

What is the Ferguson reflex?

Answer 14

A positive feedback loop to enhance labor
Primary stimulus for release of oxytocin is distention of cervix —> stimulates contractions of uterus
Uterine contractions then stimulate more oxytocin release which stimulates more contractions

Question 15

What are the effects of relaxin?

Answer 15

Cytokine structurally related to insulin
Produced by corpus luteum, placenta and decidua
Thought to play a role in keeping uterus in a quiet state during pregnancy
Max plasma concentrations weeks 38-42
-may soften and help dilate cervix
-elevated levels at 30 weeks associated with premature birth

Question 16

What mechanical changes occur during parturition?

Answer 16

Uterine size - a factor in regulating parturition
Stretch of smooth muscle increases Ferguson reflex, positive feedback and thus further contractions
Uterine stretch also increases prostaglandin production
Twins average 19 day shorter gestation

Question 17

What is necessary for the expulsion of the fetus?

Answer 17

Cervical remodeling

Structural changes resulting in a change from fetal support to birth canal

Question 18

Describe the initiation of labor

Answer 18

Placenta produces CRH (maternal levels rise during late pregnancy and labor) which promotes myometrial contractions sensitizing uterus to prostaglandins and oxytocin
Accumulates in fetal circulation and stimulates fetal ACTH secretion
Increases fetal adrenal cortisol production which stimulates further placental CRH release
Increased fetoplacental estrogen which enhances myometrial contractility

Question 19

Describe the contractions that occur during the last hours of pregnancy into labor

Answer 19

Contractions become exceptionally stronger and begin to stretch the cervix, shorten muscle cells
Retract lower uterine segment and cervix upward
Cervix becomes increasingly dilated and is drawn up to just below the pelvic inlet
Subsequent uterine contractions push fetus downward and through the pelvis
Entire process varies in duration (first stage occupies most of the time and second stage generally takes an hour)

Question 20

Describe expulsion of the placenta

Answer 20

Uterus contracts reducing the area of attachment
Separation of placenta results in bleeding and clotting
Oxytocin constricts uterine blood vessels to allow for clotting
Nipple stimulation induces oxytocin release
Synthetic oxytocin sometimes given to assist in uterine contractions

Question 21

Describe the human mammary gland

Answer 21

Contains 15-20 lobes of glandular tissue
Lobes separated by CT and adipose
Each lobe consists of lobules that contain glandular units
Lactiferous ducts collect milk from lobules to the nipple
Widens to lactiferous sinus just before the nipple
Each duct opens independently on surface

Question 22

Describe the alveolar epithelium

Answer 22

Luminal epithelium

Cells responsible for milk synthesis and secretion

Question 23

Why are myoepithelial cells?

Answer 23

Between epithelial cells and basement membrane
Contractile function
Move milk from alveoli into ducts

Question 24

Describe breast development from brith to sexual maturity

Answer 24

At brith mammary gland almost entirely lactiferous ducts with few alveoli
Apart from some branch development the breast remains in this state until puberty
Under the actions of estrogens, lactiferous ducts sprout and branch
-ends form small, solid, spheroidal masses of cells which develop into alveoli

Question 25

Describe the changes in mammary tissue as the menstrual cycle is established

Answer 25

Mammary tissue is exposed to estrogen and progesterone (induces additional ductal-lobular-alveolar growth)
Breasts increase in size (deposition of adipose and CT)
Cyclic changes to breast occurs including increase in breast volume, breast tenderness, some secretory activity may occur and involution

Question 26

Describe breast growth/development during pregnancy

Answer 26

Rapid growth and branching from the terminal ducts into the adipose stimulated by circulating hormones
As epithelial structures proliferate, adipose tissue decreases
Infiltration of interstitial tissue with lymphatic, plasma cells and eosinophils
By 3rd trimester parenchymal cell growth slows and alveoli become distended with early colostrum

Question 27

Describe the lactating mammary gland

Answer 27

Large number of alveoli (minimal CT separating them)
NE factors regulate function to establish and maintain milk secretion
Prolactin (and prolactin inhibitory factor/dopamine) and oxytocin impact lactogenesis the most with prolactin maintaining milk synthesis and oxytocin being responsible for milk ejection
Intermittent secretion of prolactin occurs during nursing

Question 28

Describe milk production

Answer 28

Alveolar epithelial cells secrete milk components by 5 main pathways
Secretory pathway, trabecular endocytosis and exocytosis, lipid pathway, transcellular salt and water transport and paracellular pathway

Question 29

What is the secretory pathway?

Answer 29

Milk proteins go through the golgi -> packaged into vesicles -> released via exocytosis into the alveolar lumen

Question 30

What is the trans cellular endocytosis and exocytosis pathway?

Answer 30

Proteins taken up by endocytosis and then move through the cell within vesicles to then be released into the alveolar lumen via exocytosis
Ex. Immunoglobulins

Question 31

What is the lipid pathway?

Answer 31

Milk lipids simply move through the cell and diffuse out into the alveolar lumen

Question 32

What is the transcellular salt and water transport pathway?

Answer 32

Salt and water move through channels and transporters to the alveolar lumen

Question 33

What is the paracellular pathway?

Answer 33

Ions and water move in between cells to make their way to the alveolar lumen

Question 34

What are the four effects of suckling on hormone release?

Answer 34

1. Suckling stimuli (or sight/sound of child) activates afferent neural pathway from breast to SC and then to hypothalamus
2. Dopamine release is inhibited (releases inhibits of lactotrophs and results in increase of prolactin which stimulates milk production)
3. Stimulation of production and release of oxytocin from posterior pituitary (interacts with myoepithelial cells resulting in milk let down)
4. Inhibition of hypothalamus GnRH production (results in decreased release of LH and FSH and inhibits the ovarian cycle)

Question 35

Describe cessation of lactation

Answer 35

When the suckling stimulus is discontinued milk accumulates
Distention and mechanical atrophy of epithelial structures; Rupture of alveolar walls; Compression of capillaries resulting in alveolar hypoxia
Cell and glandular debris are phagocytosed
Lobular-acinar structures become smaller
Ductal system predominates
Full involution can take up to 3 months

Question 36

What are the two stages of cessation of lactation (involution)

Answer 36

Apoptosis of epithelial cells

Remodeling of tissue, stroma and adipose

Question 37

Brest development at puberty depends primarily on which hormones?

Answer 37

Estrogens and progesterone

Question 38

What leads to full development of the breasts during pregnancy?

Answer 38

Gradual increases in PRL and hPL and very high levels of estrogens and progesterone

Question 39

Describe hormones affecting the breasts

Answer 39

Mammogenic (promoting the proliferation of alveolar and duct cells)
Lactogenic (promoting initiation of milk production by alveolar cells)
Galactokinetic (promoting contraction of myoepithelial cells and thus milk ejection)
Galactopoietic (maintaining milk production after it has been established)