42. Physiology of Pregnancy, Parturition, and Lactation Flashcards
What is the maternal side of the placenta, that is immediately apposed to the chorion frondosum, or fetal side of mature placenta?
Decidua basalis
3 major structures that make up the mature placenta
Chorionic villi
Intervillous space
Decidua basalis
Main functions of the placenta
Fetal “gut” supplying nutrients
Fetal “lung” exchanging O2 and CO2
Fetal “kidney” regulating fluid volume and disposing of waste
Endocrin gland synthesizing steroids and proteins that affect maternal and fetal metabolism
Endocrine functions of placenta
Maintaining pregnant state of uterus
Stimulating lobuloalveolar growth and function of maternal breasts
Adapting aspects of maternal metabolism and phys to support fetus
Regulating aspects of fetal dev’t
Regulating timing and progression of parturition
______ represent the functional unit of the placenta
Chorionic villi
[extensive branching and increased surface area for exchange]
_____ arteries from the maternal side of the placenta empty into the ______ space, which is drained by maternal veins
Spiral; intervillous
Describe maternal blood flow to fetus in terms of arterial and venous supply, as well as purpose of intervillous spaces
Arterial blood discharged from ~120 spiral aa., spurts into intervillous space
Filling of these spaces dissipates the force and reduces blood velocity
Slowing of blood flow allows adequate time for exchange of nutrients
Blood drains through venous orifices and enters placental veins (no capillaries are present!)
Principal factors regulating maternal blood flow
Geometry of blood vessels — spiral arteries are perpendicular and veins are parallel
Differences between maternal vs. fetal arterial and venous pressure
Patterns of uterine contractions — attenuate arterial inflow and interrupt venous drainage
Fetal blood flow originates from two umbilical arteries which carry ______ blood. These arteries branch and penetrate the ______ to form a chorionic villi capillary network, obtaining oxygen and nutrients and returning them to the fetus from a single umbilical vein
Deoxygenated; chorionic plate
Terminal dilations in the fetal capillary network offer _____ blood flow and thus improved exchange of nutrients
Slower
Describe pO2, pCO2, and pH of maternal blood entering the intervillous space
pO2 ~100 mm Hg
pCO2 ~40 mm Hg
pH of 7.4
[fetal pO2 is 23 umbilical aa., 30 in umbilical v.]
Diffusion of O2 into the chorionic villi causes the pO2 of blood in intervillous space to fall to 30-35 mm Hg and lower in umbilical v. of the fetus. What allows sufficient oxygen saturation in fetus?
Differences in hemoglobin structure make it higher affinity for O2, allowing sufficient Hb saturation
What drives CO2 transfer between mother and fetus?
Concentration gradient difference
Compare pCO2 in umbilical aa. vs. intervillous spaces near term
pCO2 ~48 mm Hg in umbilical aa.
pCO2 ~43 mm Hg in intervillous spaces
[concentration gradient driving CO2 to maternal side]
Describe affinity for CO2 in maternal vs. fetal blood
Fetal blood has slightly lower affinity for CO2 than maternal blood
T/F: all factors favor transfer of CO2 from fetus to mother
True
Other than concentration gradient-based passive diffusion, what are some other solute transfer mechanisms between mother and fetus?
Passive exchange (non-protein nitrogen wastes like urea/creatinine, lipid soluble hormones)
Facilitated diffusion (glucose to fetus)
Primary and secondary active transport to fetus to support growth (amino acids, vitamins, minerals)
Receptor mediate endocytosis (large molecule exchange like LDL, hormones, Abs)
2 important functions of amniotic fluid
Mechanical buffer
Fetus excretes waste products through it
How often does water in amniotic fluid “turn over”?
At least 1x/day
At >10-12 weeks, what provides 75% of amniotic fluid production?
Kidney excretions of fetus
Kidney excretions provide ~75% of amniotic fluid production, what provides the rest?
Pulmonary secretions
Fluid removal from fetus:
55% from ______
30% from ______
15% from _____
GI tract
Amnion
Lungs
The placenta plays a key role in manufacture of what biologic molecules?
Steroid hormones
Amines
Polypeptides (hormones and neuropeptides)
Proteins/glycoproteins
The placenta regulates release of local placental hormones as well as hormones into fetal or maternal circulation in _______ fashion
Paracrine
What cell type secretes hCG
Syncytiotrophoblasts
What is the significance of hCG being structurally related to LH?
It can bind LH receptors with high affinity
It rapidly accumulates in maternal circulation
How do levels of hCG change during pregnancy?
Serum levels double daily up to ~10 weeks (that’s when they are highest), then sharp followed by gradual decline
Primary function of hCG
Stimulates LH receptors in corpus luteum, preventing luteolysis
Maintains high levels of luteal derived progesterone
What hormone is thought to be responsible for nausea associated with morning sickness?
hCG
Small amounts of hCG enter male fetal circulation with what purpose?
Stimulate fetal Leydig cells to produce testosterone
What is the primary human chorionic somatomammotropin (hCS)?
Human placental lactogen (hPL)
What 2 hormones is hPL structurally related to?
Growth hormone and prolactin
What cells produce hPL?
Syncytiotrophoblast
When is hPL detected in syncytiotrophoblasts vs. in maternal serum?
Detected at day 10 in syncytiotrophoblasts and in maternal serum at 3 weeks
Functions of hPL
Coordinating metabolism of fetoplacental unit via conversion of glucose to fatty acids and ketones; can have antagonistic action to maternal insulin, contributing to GDM
Lipolytic actions help mother shift to free-fatty acid use for energy
Promotes development of maternal mammary glands during pregnancy
High levels of _____ are required throughout pregnancy for implantation and early maintenance of pregnancy
Progesterone
Where is progesterone derived from in pregnancy?
Corpus luteum
Primary functions of progesterone in pregnancy
Increased adhesion proteins in endometrium
Stimulates endometrial gland secretions for early nutrient transfer
Reduces uterine motility
Inhibits propagation of uterine contractions
Induces mammary growth and differentiation
What hormone is responsible for inducing endometrial growth, progesterone receptor expression, and LH surge just prior to ovulation?
Estrogen
Functions of estrogen:
Increases _____ blood flow
Increases _____ receptor expression in syncytiotrophoblasts
Induces _____ and ______ receptors necessary for parturition
Increases growth and development of ______ glands
Uteroplacental
LDL
Prostaglandins; oxytocin
Mammary
How do levels of hPL change throughout pregnancy
Gradual rise until parturition
How do levels of progesterone change throughout pregnancy
Gradual rise until parturition
How do levels of estrogen change throughout pregnancy
Gradual rise until parturition
Estradiol levels are highest, estriol exceeds estrone starting at around 30 weeks
T/F: during pregnancy, maternal levels of progesterones and estrogens decline to levels substantially lower than during a normal menstrual cycle
False; they are much higher than normal menstrual cycle
The placenta is an imperfect organ and cannot produce estrogens and progesterone along, so coordination between maternal, placental, and fetal tissues are required. The mother is responsible for supplying _____ for hormone production; the fetal _____ and ______ supply enzymes that the placenta lacks
Cholesterol; adrenal gland; liver
What enzymes for estrogen production are provided by the placenta?
3B-hydroxysteroid dehydrogenase
Aromatase
Sulfatase
What enzymes are provided by the fetus for estrogen production?
17a-hydroxylase
17,20-desmolase
16a-hydroxylase
A luteal-placental shift occurs around week ____ in terms of progesterone production. Its production is largely unregulated. Syncytiotrophoblasts import ____ from maternal blood; they express CYP11A1 and 3B-HSD1
Progesterone is released primarily into ______ compartment, thus maternal serum levels _____ throughout pregnancy
8; cholesterol
Maternal; rise
T/F: the placenta produces cholesterol
False, it cannot produce cholesterol
The placenta lacks 17a-hydroxylase and 17,20 desmolase needed for estrone and estradiol, as well as 16a-hydroxylase needed for estriol. What overcomes this?
The maternal-placental-fetal unit —
Mother supplies cholesterol
Fetal adrenal gland and liver supply enzymes needed, also produce DHEAS and 16a-OH-DHEAS (weak androgens)
T/F: the fetus avoids high levels of steroid hormones
True — the fetus lacks 3B-hydroxysteroid dehydrogenase and aromatase, thus no estrogen production
Fetus conjugates steroid intermediates to sulfate, reducing their activity
What organ completes the steroidogenesis of estrogens?
Placenta
The fetus conjugates steroid intermediates to sulfate, reducing their activity. So in the production of estrogen, _______ travels from the placenta to fetus. DHEA and 16a-hydroxyl-DHEA are _____while in fetus. As the DHEA and 16a-hydroxyl-DHEA-S move into the placenta, a ______ removes the sulfate groups. The placenta then completes steroidogenesis of estrogens
Pregnenolone; sulfated; sulfatase
Mean duration of human pregnancy
~266 days (38 weeks) from ovulation
Or ~280 days (40 weeks) from day 1 menstrual cycle
How does maternal blood volume change in response to pregnancy?
Blood volume increases
Total plasma volume increases 40-50%
Begins to increase in 1st trimester, rapid increase in 2nd and 3rd trimester
What system mediates the increase in maternal blood volume in response to pregnancy?
Renin-angiotensin-aldosterone system (augments renal reabsorption of salt and water)
How do maternal RBCs change in response to pregnancy? How does this affect hematocrit
RBC increase of 20-30%, mediated by increases in erythropoitin
Net result is a decrease in hematocrit
How does maternal cardiac output change in response to pregnancy?
Increased blood volume results in increase in heart rate (~15 bpm)
CO increases appreciably in 1st trimester, with slight increase at 2nd and 3rd trimester (overall 45% increase)
Increase in CO reflects mainly an increase in stroke volume but also heart rate
How does maternal mean arterial pressure change in response to pregnancy? Why?
Despite increase in plasma volume, MAP decreases mid-pregnancy with a rise during 3rd trimester (but still remaining lower than normal)
This is due to decrease in peripheral vascular resistance because of vasodilating effects of progesterone and estrogen
How does the increasing progesterone during pregnancy affect alveolar ventilation in the mother?
Increases it
Overall little effect on respiratory rate
Tidal volume increases markedly — 40% (decreases CO2 levels in maternal blood)
As fetus grows in late pregnancy, displacement of diaphragm can occur so lung expansion decreases
Maternal tidal volume markedly increases in pregnancy, thus decreasing CO2 levels in maternal blood. What condition can this lead to, and how is it compensated?
Mild respiratory alkalosis can occur; compensated for by kidney lowering plasma bicarb
In the maternal response to pregnancy there is an increased demand for what 3 dietary nutrients in particular?
Protein — need additional 30g/day for growth
Iron — need net gain of 800 mg circulating iron for expanding Hb mass (nonpregnant woman absorbs 1.5mg/day, pregnant woman requires 7mg/day)
Folate — increase in blood cells
A deficiency in folate in pregnancy leads to what type of birth defects?
Neural tube defects
Maternal GI tract changes in pregnancy
Morning sickness (usually resolves by 20 weeks when hCG decreases)
Mechanical changes — stomach displacement, changes in esophageal sphincter tone can lead to acid reflux
Decreased colonic motility — increased water absorption; constipation
What happens to maternal insulin in early pregnancy?
Increased secretion and sensitivity
What happens to maternal insulin response in the 2nd and 3rd trimester? Why?
Maternal insulin resistance develops
Shunts glucose to fetus; due to hPL, hGH, progesterone, cortisol, and prolactin
If insulin resistance in mother is too high, GDM can develop, resulting in increased maternal BG, as well as what changes in fetus?
Increased fetal glucose uptake and BG —> increased growth of fetus, chemical and cellular imbalances after birth - hypoglycemia, jaundice, polycythemia, and hypocalcemia
Human birth usually occurs at _____ weeks gestation, which is ______ weeks fetal age
~40; 38
Parturition involves:
transformation of the myometrium from quiescent to highly ______
Remodeling of the uterine _____ such that it softens and dilates
Rupture of fetal ______
Expulsion of uterine contents and return of uterus to prepregnant state
Contractile
Cervix
Membranes
What is the obstetric definition of labor?
Series of regular, rhythmic, and forceful contractions that develop to facilitate thinning and dilation of the cervix — these may last for several hours, a day, or even longer and eventually result in expulsion of fetus, membranes, and placenta
Once labor is initiated, it is sustained by a series of ____ feedback mechanisms
Positive
Parturition occurs in distinct stages 0-3. What is associated with stage 0?
Uterine tranquility and refractoriness to contraction
Parturition occurs in distinct stages 0-3. What is associated with stage 1?
Uterine awakening, initiation of parturition, extending to complete cervical dilatation
Parturition occurs in distinct stages 0-3. What is associated with stage 2?
Active labor, from complete cervical dilatation to delivery of newborn
Parturition occurs in distinct stages 0-3. What is associated with stage 3?
From delivery of fetus to expulsion of the placenta and final uterine contraction
Stage 1 of parturition involves uterine awakening, initiation of parturition, extending to complete cervical dilatation. What physiological changes are associated with this stage?
Increase in number of gap junctions between myometrial cells; increase in number of oxytocin receptors
During stage 0 of parturition, which constitutes most of pregnancy, the uterus is relaxed and relatively insensitive to hormones that stimulate contractions such as ___ and _____
Prostaglandins; oxytocin
During stage 0 of parturition, uterine myometrial cells undergo significant _________
Weak, irregular contractions known as ____ ____ contractions occur towards the end of pregnancy; these are not powerful enough to induce labor and are thought to prepare the uterus for parturition
Hypertrophy
Braxton hicks
What happens to uterine excitability towards the end of pregnancy?
Increases; will develop strong rhythmical contractions to expel conceptus
This is due to progressive hormone and mechanical changes
Prior to labor, the myometrium transforms to a more contractile state. What stage of parturition is this associated with?
Stage 1 = transformation/activation
Stage 1 of parturition involves production of contraction-associated hormones and proteins. What are some examples of these?
Prostaglandin F2a receptors
Oxytocin receptors
Enzymes involved in prostaglandin synthesis
Enzymes that breakdown collagen matrix in cervix
Components of gap junctional complexes
During stage 1 of parturition, components of gap junctional complexes increase; why are these especially important?
Because they form electrochemical connections between myometrium cells to synchronize the contractions
Induction of active labor occurs in stage 2 of parturition. What are the 3 major factors that induce contractions?
Increased levels of prostaglandins (especially PGF2a)
Increased myometrial interconnectivity
Increased myometrial responsiveness to prostaglandins and ocytocin
Contractions that begin in stage 2 force the fetal head against the _____, which becomes progressively compliant as the ________ remodels.
Eventually enough dilation occurs to allow fetus through
Cervix; ECM
Reciprocal changes in uterine progesterone and estrogen receptors are necessary for onset of labor. Progesterone typically promotes myometrial ______ during pregnancy, and _____ contractions of labor
Relaxation; blocks
Nuclear _______ antagonists are drugs that increase myometrial contractility/excitability and can induce labor at any stage of pregnancy
Progesterone
At the onset of labor, there is a desensitization of uterine cells to the actions of progesterone. This leads to an increase in _____ receptor expression, thus augmenting myometrial contractility and thus cervical dilation
Estrogen
Estrogens oppose the action of progesterone by increasing responsiveness to ____ and _____, stimulating formation of gap junctions and increasing numbers of oxytocin receptors in myometrium and _____ tissue
There is also an increase in production/release of prostaglandins by fetal _____
Oxytocin; prostaglandins; decidual
Membranes
Actions of prostaglandins in labor
Strongly stimulate myometrial contraction; believed to initiate labor
Large doses of what 2 prostaglandins evokes myometrial contractions at any stage of gestation?
PGF2a
PGE2
PGF2a potentiates ______-induced contractions by promoting formation of gap junctions
Oxytocin
Prostaglandins stimulate the ______ of the cervix in early labor. Their metabolic products increase in blood and ______ just before and during labor
Effacement
Amniotic fluid
Prostaglandin synthesis is stimulated by what 3 factors?
Estrogen in fetal membranes
Oxytocin in uterine cells
Uterine stretch
The uterus is insensitive to oxytocin until ____ weeks
20
What hormone increases oxytocin receptors?
Estrogen
Estrogen increases oxytocin receptors in _____ _____ for smooth muscle contraction, as well as receptors in ____ ____ to stimulate PGF2a production
Uterine myometrium; decidual tissue
T/F: Oxytocin receptors increase to 80x higher than baseline by 36 weeks, and increase to 200x by early labor
True
What hormone is released in bursts during active labor
Oxytocin
[frequency increases as labor progresses]
What is the primary stimulus for oxytocin release?
Distention of cervix
The primary stimulus for oxytocin release is distention of the cervix, this is known as the ______ reflex — a ______ feedback loop to enhance labor
Ferguson; positive
_______ = cytokine structurally related to insulin, produced by the corpus luteum, placenta, and decidua thought to play a role in keeping the uterus in a quiet state during pregnancy
Relaxin
During what weeks of pregnancy would you expect maximal plasma concentrations of relaxin? Why?
38-42
May soften and help dilate cervix; elevated levels at 30 weeks are associated with premature birth
Describe uterine size as a factor in the mechanical changes regulating parturition
Stretch of smooth muscle of uterus increases the Ferguson reflex positive feedback —> further contractions
Uterine stretch also increases prostaglandin production
[twins average 19 day shorter gestation due in part to the increased stretch leading to the above factors]
The signals for initiation of labor are not completely understood. The placenta produces _______, and maternal levels of this rise during late pregnancy and labor, promoting myometrial contractions and sensitizing the uterus to prostaglandins and oxytocin
CRH
CRH accumulates in fetal circulation and stimulates fetal ______ secretion
ACTH
CRH accumulates in fetal circulation and stimulates fetal ACTH secretion.
This increases fetal production of ______ ______ which stimulates further placental CRH release
It also increases fetal production of _______ _______, which enhances myometrial contractility
Adrenal cortisol
Fetoplacental estrogen
Throughout most of pregnancy, the uterus undergoes periodic episodes of weak and slow contractions = braxton hicks contractions.
These become exceptionally strong during the last hours of pregnancy into active labor. Describe the actions of uterine contractions
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
Describe the postive feedback involved in maintaing labor
Positive feedback loops involving prostaglandins from uterine wall, oxytocin from posterior pituitary, and uterine contractions themselves sustain labor once it has started
Uterine contractions stimulate prostaglandin release, which increases the intensity of uterine contractions
Uterine activity stretches the cervix which stimulates oxytocin release through ferguson reflex
During parturition, the fully dilated cervix is drawn up just below the ________. Subsequent uterine contractions push the fetus downward and through the pelvis
The entire process varies in duration, but the ______ stage occupies most of the time. The _____ stage generally lasts less than 1 hr
Pelvic inlet
First; second
_____ ____ = refers to where the presenting part of the fetus is in the pelvis relative to ischial spines
Fetal station
The fetal station is usually based on the baby’s _______, and is measured from -3 to +3
Head
When the fetal station = 0 station, the presenting part is even with the ___ ____
Ischial spines
[baby is said to be “engaged” when largest part of head enters pelvis]
If the presenting part of the fetus lies above the ischial spines, the station is reported as a ____ number
Negative
Phases of fetal delivery
Dilation and effacement
Descent and expulsion
Expulsion of placenta
______ is the process by which the cervix prepares for delivery, measured in percentages: at 50% the patient is halfway, 100% the cervix is paper thin and labor is right around the corner
Effacement
Describe dilation of cervix, direction of contractions, and average duration of descent and expulsion phase of delivery
Cervix fully dilated to 10 cm
Contractions are strongest at top pushing fetus downward
Avg 20-50 min duration
Describe expulsion of placenta
Uterus contracts, reducing area of attachment
Separation of placenta results in bleeding and clotting. Oxytocin constricts uterine blood vessels. Nipple stimulation induces oxytocin release. Synthetic oxytocin is sometimes given to assist in uterine contractions
One complication of labor/delivery is prolonged labor — which is defined as labor lasting more than ____-____ hrs.
Multiple types are distinguished based upon what 2 factors?
18-24
- based upon which stage of labor is prolonged (latent phase, cervical dilation per hour, prolonged deceleration, secondary arrest of dilation, protracted descent, arrest of descent, prolonged second stage)
- time variability in nulliparous vs. multiparous women
Prolonged labor can be characterized based on whether the mother is multiparous or nulliparous. Which one requires less time for diagnosis of prolonged labor?
Multiparous — labor is expected to proceed slightly more quickly
Main causes of prolonged labor
Poor uterine contractions
Baby’s position or size is abnormal
Issues with pelvis or birth canal
Obstructed labor is also known as labor ____
Dystocia
Describe labor dystocia
Even though uterus is contracting normally, the baby does not exit the pelvis during childbirth due to being physically blocked
Common causes of labor dystocia
Breech presentation
Macrosomia (baby is too large)
Occiput posterior (fetus face-up)
Malpresentation - fetal head is not perfectly flexed
Compound presentation - 2 parts presenting
Congenital abnormalities obstructed in birth canal
Variations in breech presentation
Complete breech
Incomplete (footling - buttocks first with one leg extended)
Frank breech (legs extended, buttocks first)
Possible causes for breech presentation
Large baby
No fluid
Birth defects
Uterine anomalies
Risks of labor from breech presentations
Fetal injury
Cord prolapse
Cord entrapment
Maternal injury
Delivery options for breech presentation
Vaginal breech delivery
External cephalic version (ECV)
Elective C-section
One possible complication of labor/delivery is ruptured uterus in which integrity of myometrial wall is breached. This can be spontaneous or traumatic in nature and typically occurs in active labor, but can occur during late pregnancy.
What are risk factors/causes of ruptured uterus?
Uterine scar from previous C-section, dysfunctional/prolonged labor, labor augmentation by oxytocin or prostaglandins, excessive manual pressure applied to fundus during delivery
Signs/symptoms of ruptured uterus
Abdominal pain and vaginal bleeding
Deterioration of fetal HR (leading sign)
Loss of fetal station on manual vaginal exam (cardinal sign)
Intra-abdominal bleeding leading to hypovolemic shock
Preterm labor is defined as labor beginning before the ____ week of pregnancy
37th
[this occurs in 12% of all pregnancies; uterine contractions cause the cervix to open earlier than normal]
Possible medical risk factors for preterm labor
UTIs
Uterine or cervical abnormalities
Chronic illness (HTN, kidney disease, diabetes, etc.)
Lifestyle risk factors: smoking, drinking alcohol, drug abuse, high levels of stress, etc.
Condition characterized by high blood pressure and signs of damage to another organ system during pregnancy, often the kidneys
Preeclampsia
Preeclampsia occurs after week ____ of pregnancy and affects at least 5-8% of pregnancies.
20
Other than high blood pressure, what other symptoms typically accompany preeclampsia?
Proteinuria
Generalized edema
Causes of preeclampsia
No definitive known cause!
Likely multifactorial: abnormal placentation, immunologic factors, prior maternal pathology like HTN, obesity, and hx of preeclampsia
Disease of the placenta is thought to be involved in preeclampsia — thought to be associated with limited blood supply to ______ aa., causing ischemia and endothelial damage with release of cytokines
Uterine
T/F: The placenta of women with preeclampsia is abnormal and characterized by poor trophoblastic invasion
True
If preeclampsia is left untreated, it can lead to serious or fatal complications for both the mother and baby —> eclampsia. What signs/symptoms are associated with eclampsia?
HELLP:
Hemolysis
Elevated Liver enzymes
Low Platelet count
Mechanism thought to be responsible for preeclampsia
Deficient trophoblast invasion of spiral aa. —> decreased placental blood flow —> placental ischemia —> placental release of factors leading to endothelial activation/dysfunction —> decreased renal pressure natriuresis and increased TPR —> HTN
The mammary gland consists of 15-20 lobes, composed of glandular tissue, as well as fibrous and _____ tissue.
Each lobe is made up of what components?
Adipose
Alveoli, blood vessels, lactiferous ducts
Describe the alveolar walls associated with mammary glands for lactation
Single layer of cuboidal to columnar epithelial cells — depending on fullness of alveolar lumen
The luminal epithelium associated with mammary glands is called _____ epithelium; these cells are responsible for milk synthesis and production
This epithelium is surrounded by _______ cells, which exist between the epithelial cells and basement membrane. They have contractile function and move milk from alveoli into ducts
Alveolar
Myoepithelial
When fully developed, the the lobules of the mammary glands consist of rounded ______, which open into the smallest branches of milk-collecting ducts. These, in turn, unite to form larger _______ ducts, each draining a lobe of the gland. The lactiferous ducts converge towards the _____ of the nipple (or papilla) beneath which they form dilations, or _______ ______, that serve as small reservoirs for milk.
After narrowing in diameter, each lactiferous sinus runs separately through the nipple to open directly on its surface. Also opening onto the peripheral area of the areola are small ducts from the ______ glands, which are large sebaceous glands whose secretions probably have a lubricative function during suckling
Alveoli; lactiferous; areola; lactiferous sinuses
Montgomery
The breast consists of a series of secretory lobules which empty into ductules. Ductules form from 15-20 lobules which combine into a duct, which widens at the ______
The lactiferous duct carries secretions to outside
Ampulla
Describe mammary glands at birth. How does this change leading up to puberty?
Almost entirely composd of 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
As the menstrual cycle is established, mammary tissue is exposed to ____ and ______ which induces additional ductal-lobular-alveolar growth
Estrogen; progesterone
During puberty, breasts increase in size due to increased deposition of ___ and ____ tissue
Adipose; connective
What are the cyclical changes to breasts that occur with puberty and establishment of menstrual cycle?
Increase in breast volume
Breast tenderness
Some secretory activity may occur
Involution
Breast development at puberty depends primarily on estrogens and progesterone.
During pregnancy, gradual increases in ____ and ____, and very high levels of estrogen and progesterone lead to full development of breasts
PRL; hPL
______ hormones promote proliferation of alveolar and duct cells
________ hormones promote initiation of milk production by alveolar cells
Mammogenic
Lactogenic
_______ hormones promote contraction of myoepithelial cells, and thus milk ejection
_______ hormones maintain milk production after it has been established
Galactokinetic
Galactopoietic
Examples of mammogenic hormones (promote cell proliferation)
Lobuloalveolar growth: estrogen, growth hormone, cortisol, prolactin
Ductal growth: estrogen, growth hormone, cortisol, relaxin
Examples of lactogenic hormones
Prolactin hCS (or hPL) Cortisol Insulin Thyroid hormones Withdrawal of estrogen+progesterone
Galactokinetic hormones
Oxytocin
Vasopressin
Galactopoietic hormones
Prolactin (primary)
Cortisol and other metabolic homrones (permissive)
By midpregnancy, duct and lobule proliferation is complete and differentiation of alveolar cells occurs.
Lactogenesis is inhibited by ____ and _____ which render mammary cells unresponsive to prolactin
Small amounts of _____ are produced in late pregnancy, which is a thin, yellowish milk secreted the first few days after parturition containing a high concentration of immunoglobulins
Estrogen; progesterone
Colostrum
Following parturition, there is a drop is steroid hormones. In the absence of suckling, how long will milk secretion last?
3-4 weeks
Following parturition, suckling stimulates prolactin secretion via a neuroendocrine reflex. The amount released depends on duration and strength of suckling.
Suckling inhibits hypothalamic ____ neurons
Dopaminergic
Classic lactogenic hormone structurally related to GH, having mammogenic, lactogenic, and galactopoietic effects
Prolactin
Feedback from prolactin decreases dopamine release, as well as ____ release, which results in decreases in LH and FSH
What does this mean for resuming menstrual cycles after parturition?
GnRH
High levels of prolactin may lead to lactational amenorrhea
____enhances milk ejection by stimulating contraction of network of myoepithelial cells surrounding alveoli and ducts of breast (thus it has galactogenic effect)
Oxytocin
Alveolar epithelial cells secrete milk components by what 5 main pathways?
- Secretory pathway
- Transcellular endocytosis and exocytosis
- Lipid pathway
- Transcellular salt and water transport through channels+transporters
- Paracellular pathway for ions and water
Describe secretory pathway for milk production
Lactalbumin and casein synthesized in ER
Ca and phosphate added to lumen of golgi
Lactose synthetase in lumen of golgi catalyzes lactose synthesis
Water enters secretory vesicles by osmosis
Describe transcellular endocytosis and exocytosis pathway for milk production
Maternal immunoglobulins (primarily IgA) taken up by endocytosis through basolateral membrane
Then transported to apical membrane and secreted via exocytosis
Describe lipid pathway for milk production
Fats that are predominant in milk (FA chains >16 carbons) originate from diet or fat stores in surrounding adipose
FAs form lipid droplets which move to apical membrane
As the apical membrane surrounds the droplets and pinch off, milk lipids are secreted to lumen in membrane bound vesicles
Describe transcellular salt and water transport mechanism of milk production
Various transport processes at apical and basolateral membranes move small electrolytes from interstitial fluid into alveolar lumen
Water follows an osmotic gradient generated primarily by lactose and some from electrolytes
Paracellular pathway for milk production
Salt and water can also move into lumen of alveolus through tight junctions
Cells, primarily leukocytes, squeeze between the cells and enter the milk
Neurons from spinal cord stimulate production and release of oxytocin from ___ and ___nuclei in response to suckling
Paraventricular; supraoptic
4 effects of suckling on hormone release
- Activates afferent neural pathway from breast to spinal cord, then to hypothalamus
- Inhibition of dopamine release
- Spinal cord neurons stimulate production and release of oxytocin from posterior pituitary
- Spinal cord neurons inhibit arcuate and preoptic area of hypothalamus causing decrease in GnRH production, ultimately inhibiting 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 mos
