Parturition And Lactation Flashcards
When does human birth usually occur?
At 40 weeks of gestation (38 weeks fetal age)
What does parturition involve?
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
Describe the changes in uterine activity that occur during pregnancy
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
What are Braxton Hicks contractions?
Weak irregular contractions that occur towards the end of pregnancy
Not powerful enough to induce labor
Thought to prepare the uterus for parturition
What are the two major categories of effects that lead up to the intense contractions of parturition?
Progressive hormone changes
Progressive mechanical changes
Which hormones are invovled in the hormonal changes that lead up to the intestine contractions of childbirth?
Progesterone, estrogens, prostaglandins, oxytocin, relaxin
Reciprocal changes in which uterine hormone receptors are necessary for onset of labor?
Progesterone and estrogens
What are the effects of progesterone?
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
What are the effects of estrogen?
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)
What are the effects of prostaglandins?
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
What stimulates synthesis of prostaglandins?
Estrogen in fetal membranes, oxytocin in uterine cells, uterine stretch
What are the effects of oxytocin?
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
What hormonal changes occur during active labor?
Oxytocin stimulates uterine contractions that sustain labor
Stimulates PGF2a production in decidual cells
Released in bursts during active labor (frequency increases as labor progresses)
What is the Ferguson reflex?
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
What are the effects of relaxin?
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
What mechanical changes occur during parturition?
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
What is necessary for the expulsion of the fetus?
Cervical remodeling
Structural changes resulting in a change from fetal support to birth canal
Describe the initiation of labor
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
Describe the contractions that occur during the last hours of pregnancy into labor
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)
Describe expulsion of the placenta
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
Describe the human mammary gland
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
Describe the alveolar epithelium
Luminal epithelium
Cells responsible for milk synthesis and secretion
Why are myoepithelial cells?
Between epithelial cells and basement membrane
Contractile function
Move milk from alveoli into ducts
Describe breast development from brith to sexual maturity
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
Describe the changes in mammary tissue as the menstrual cycle is established
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
Describe breast growth/development during pregnancy
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
Describe the lactating mammary gland
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
Describe milk production
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
What is the secretory pathway?
Milk proteins go through the golgi -> packaged into vesicles -> released via exocytosis into the alveolar lumen
What is the trans cellular endocytosis and exocytosis pathway?
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
What is the lipid pathway?
Milk lipids simply move through the cell and diffuse out into the alveolar lumen
What is the transcellular salt and water transport pathway?
Salt and water move through channels and transporters to the alveolar lumen
What is the paracellular pathway?
Ions and water move in between cells to make their way to the alveolar lumen
What are the four effects of suckling on hormone release?
- Suckling stimuli (or sight/sound of child) activates afferent neural pathway from breast to SC and then to hypothalamus
- Dopamine release is inhibited (releases inhibits of lactotrophs and results in increase of prolactin which stimulates milk production)
- Stimulation of production and release of oxytocin from posterior pituitary (interacts with myoepithelial cells resulting in milk let down)
- Inhibition of hypothalamus GnRH production (results in decreased release of LH and FSH and inhibits the ovarian cycle)
Describe cessation of lactation
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
What are the two stages of cessation of lactation (involution)
Apoptosis of epithelial cells
Remodeling of tissue, stroma and adipose
Brest development at puberty depends primarily on which hormones?
Estrogens and progesterone
What leads to full development of the breasts during pregnancy?
Gradual increases in PRL and hPL and very high levels of estrogens and progesterone
Describe hormones affecting the breasts
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)
