86 - Pregnancy Flashcards
What is the first hormone secreted by syncytiotrophoblasts during pregnancy?
hCG
- Spikes at 10 weeks gestation
What receptors does hCG bind?
Where?
Why?
Binds to LH receptors on corpus luteum and keeps it viable (recall, LH is inhibited at this point by high P, E, and inhibin)
What hormone is responsible for nausea/morning sickness in pregnancy?
hCG
Besides binding LH receptors and keeping the fetus viable, what else does hCG do? (2)
- Stimulates fetal Leydig cells and fetal adrenal cortex
- Negative feedback actions on maternal HPG axis
What does hPL stand for?
What’s another name for it?
- Human placental lactogen
- hCS (human chorionic somatomammotropin)
(increases throughout gestation)
What 2 hormones are hPL structurally similar to?
PRL and GH
*How is hPL similar to GH, besides structure? (3)
- Counter-regulatory to insulin (anabolic and lipolytic)
- Mobilizes glucose for fetal use
- Stimulates fetal IGF-I
How is hPL similar to PRL, besides structure? (1)
Stimulates mammary gland development
The 1st 1/2 of pregnancy is considered an __________ state, and the 2nd 1/2 a __________ state.
- Anabolic (get nutrients)
- Starvation (so fetus can grow)
What pregnancy-related hormones cause pregnancy to be considered an “insulin resistant state”?
- hPL, E, and P4
cortisol as well
Where is hPL produced?
Placenta
Is hPL essential for pregnancy?
No
hPL potentiates anti-insulin actions in the mother.
Why does it increase lipolysis?
Why does it increase proteolysis?
- Lipolysis: FA’s for maternal use
- Proteolysis: AA’s for fetal use
What is the prognosis for pts w/gestational diabetes?
Usually resolves with end of pregnancy, but up to 50% will go on to develop T2DM.
What hormones are responsible for gestational diabetes?
Caused by anti-insulin effects of hPL, progesterone, prolactin, and cortisol
What are the risk factors for gestational diabetes?
- Over age 25
- Family hx of diabetes
- Certain ethnic groups (e.g. native americans)
The placenta provides a semi-protective barrier from maternal factors.
Name as many of the functions of the placenta as you can. (5)
- Supportive: provides nutrients for fetal growth
- Immune: prevents rejection of fetus by mom
- Endocrine: hormones
- Gas exchange (O2, CO2)
- Regulates fluid levels, waste disposal
What (2) placental cell types secrete hormones? (they act in a hypothalamo-pituitary manner)
- Cytotrophoblasts
- Syncytiotrophoblasts
Why is the placenta considered an “imperfect endocrine organ”?
Lacks critical enzymes to complete many steps in steroid hormone synthesis.
- This helps protect fetus from cortisol and high gonadal hormone levels
(still makes almost all hormones we’ve talked about, but not PRL, androgens, cortisol…)
What provides cholesterol to the fetus?
The mother (NOT the placenta)
What adrenal enzyme does the placenta lack?
What, therefore, can it not do?
- CYP17
- Can’t create androgens or cortisol
Because it lacks CYP17, what (fetus, mother, or placenta) converts progesterone to androgens and other steroids?
Fetus
fetus produces mostly androgens
How is E3 (estriol) formed during pregnancy?
Placenta cant make it, so fetus makes DHEAS precursor that goes to the placenta to be converted to E3.
What happens to most cortisol in the fetus?
Converted to cortisone (inactive) by 11beta-HSD2
- Protects fetus
What is fetal ACTH’s effect on placental CRH?
Stimulates (positive feedback loop of steroid hormone synthesis)
Which of the fetal adrenal zones is the biggest?
“Fetal zone” (future ZR)
- Makes adrenal androgens throughout gestation
Do we see E in the fetus?
Why or why not?
No, could disrupt its development.
What does relaxin do?
- Inhibits myometrial contractions (ensure uterine quiescence in early pregnancy)
- Relaxes pelvic bones and ligaments and softens cervix
Where is relaxin produced? (2)
- Corpus luteum (in response to hCG)
- Placenta
Where is PRL produced?
Maternal pituitary only (NOT placenta)
What does PRL do, and how are its affects altered by E and P4? (read first time)
- Essential for mammotrophic effects of E and P4
- Stimulates lactogenic apparatus during gestation, but significant lactation is inhibited by high levels of P4 and E
- E stimulates growth of the lactotrophs and increases PRL secretion
What are the cardiovascular changes seen during pregnancy?
- ^ CO (^ HR + ^ SV)
- MSP decreases, TPR decreases more than CO increases.
- Catecholamines mediate chronotropic and inotropic increases
- Some CM
- Pulmonary pressures stays the same, off setting the increase in volume with a decrease in resistance
- Venous pressure increases, 150% venous distension
What are the regional blood flow changes seen during pregnancy?
(Uterus? Skin? Kidney?)
- Uterus: may receive 30% of CO (spiral aa. ^ diameter)
- Skin blood flow increases to maintain body temperature
- Kidney blood flow increases and GFR increases
What are the blood changes seen during pregnancy?
What hormone mediates the change?
- Increase in blood volume: 50% increase in 2nd trimester, mediated by P4, anticipates hemorrhage. Both plasma and - RBC increase (via cortisol), with a net decrease in Hct.
What are the respiratory changes seen during pregnancy?
- Diaphragm is elevated by about 5 cm (reduction in expiratory reserve)
- Increase in tidal volume with no change in respiratory frequency (deeper breaths)
- Increased tidal volume results in increased alveolar ventilation
(“functional alkalosis”)
What are the GI changes seen during pregnancy?
- An additional 30g of protein per day are required
- Constipation
- GERD
What are the endocrine changes seen during pregnancy?
- HPG axis is suppressed by high concentrations of placental sex steroids.
- There is a growth of pituitary lactotrophs and an increase in PRL secretion (GnRH suppression).
What are the metabolic changes seen during pregnancy? (summarize 1st vs. 2nd 1/2 of preg)
First half of pregnancy: mother is in anabolic state
- Nl or ^ sensitivity to insulin
- Increased fat deposition, glycogen stores
- Promotes breast growth in mother and allows her to “stockpile”” nutrients to meet the demands of the enlarging fetus.
Second half of pregnancy: “accelerated starvation,” catabolic state characterized by insulin resistance.
- Mediated by hPL
- Increased plasma glucose and fatty acid levels
What is parturition?
The action of giving birth
Before labor starts, what hormone keeps the uterus inactive?
Progesterone
Briefly, what are the 3 phases of labor?
- Activation of the uterus
- Positive feedback phase
- Evacuation of the uterus
What is the Ferguson reflex?
Uterine stretch from mature fetus stimulates oxytocin, which stimulates more stretching, which stimulates more OXY (positive feedback loop)
What occurs during phase 1 of labor? (activation of the uterus)
(What HPA axis hormone peaks?)
- Release from inhibitory actions of P4
- Ferguson reflex
- Fetal HPA axis is activated – CRH levels peak
What occurs during phase 2 of labor? (positive feedback)
- Widening (dilation) and thinning (effacement) of cervix
What occurs during phase 3 of labor? (evacuation of the uterus)
- Expulsion of fetus from uterine compartment and 2. release of placenta
The initiation and maintenance of labor and uterine
evacuation are influenced by P4, E2, cortisol, relaxin, oxytocin, CRH, prostaglandins, catecholamines. The most dominant of these is the decrease in ______________ and increase in _______________.
- Progesterone
- Estradiol
Recall: how many AA’s is OXY?
9 AAs
______________ increases the number of OT receptors in myometrial tissues in pregnancy, increasing the potency of a given concentration of OT.
(OT = oxytocin)
Estrogen
When is the uterus most sensitive to OT?
During labor
What is pitocin?
Synthetic OT used to induce labor
Besides the Ferguson reflex, what other reflex involves OT?
Suckling on breast (another feedback loop)
What does OT stimulate the release of that also causes uterine contractions?
Prostaglandins
What other roles does OT have during birth besides Ferguson reflex and prostaglandins?
- Promotes hemostasis of expelled placenta vessels.
- Stimulates maternal behaviors postpartum (important for maternal bonding)
Besides OT, what else leads to increased local prostaglandins that leads to an increase in myometrial cell Ca2+, yielding more forceful myometrial cell contractions?
Decrease in the progesterone/E2 ratio
What changes signal the ability for the mother to begin lactating?
Placenta no longer present, so decreased P4 and E2
What hormone is high during milk secretion?
PRL
What hormones does breast suckling stimulate the release of?
PRL, OT
What other hormone does PRL affect?
Inhibits GnRH
What other things does PRL affect besides lactation?
Like OT, stimulates maternal behavior during pregnancy and after parturition
Mammary gland development is initiated at puberty through the action of __________ (hormone) and growth factors.
What hormones lead to its further differentiation during pregnancy?
E2
- E2, PRL, hPL
Lactation is inhibited by high ____________ (hormone) during pregnancy.
P4
What’s the name of the first breast milk produced?
How is it different from other types of milk?
Colostrum
- Less fat, higher protein
(cow milk very high in calcium)
What 3 hormones are essential for continued milk production?
PRL, cortisol, insulin
An infant’s cry can lead to the production of what hormone by the mother?
OT
- Increased contraction of myoepithelial cells, alveoli and smooth muscle of duct walls causes “milk letdown” for infant.
What are the 2 overall effects of PRL?
Mammogenic effects, galactogenic effects
What are the 3 non-endocrine and non-drug methods of contraception?
- Abstinence
- Coitus interruptus
- Barriers
What is abstinence? (detail)
Natural family planning: periodic abstinence from intercourse during the fertile period surrounding the time of ovulation (”rhythm method”)
What is coitus interruptus?
Withdrawal before ejaculation
What are some barriers?
Condoms, diaphragms, sponge, and cervical caps in combination with spermicides
How does BCP work? (just read)
At what levels does it work?
Why is it good for controlling heavy menstrual bleeding?
Multiple levels:
- Acts on CNS and urogenital tract to inhibit reproductive function
- Pituitary and Hypothalamus: prevents LH surge and ovulation
- Basal gonadotropin levels are decreased
- Ovary: follicular growth is inhibited
- Fallopian tube motility decreased
- *Glandular atrophy in uterine endometrium: why it is good for controlling heavy menstruation
- Inhibits implantation of blastocyst
- Causes thick cervical mucus: inhibits sperm motility and migration
Progestational hormone prevents _____________ secretion.
LH (including blocking LH surge)
Estrogenic hormone inhibits _____________ release.
FSH
- Estrogen also stabilizes endometrium and potentiates progestin action.
What are some of the benefits of using contraceptives, besides not having a baby?
- Tx of excessive menstrual bleeding
- Protection for pelvic inflammatory disease
- Dysmenorrhea
- Hormone replacement therapy in postmenopausal women
What are some of the risks and side-effects of contraceptives?
- Contraindicated in heavy smokers over 35 and those with a history of estrogen-dependent breast carcinomas
- HTN, myocardial infarction, stroke
- Blood clots
- Depression
- Decreased libido
To define female puberty, which of the “arche” occurs before which other “arche”?
Thelarche before menarche
- Breast buds tend to develop before periods
Menarche (first menses) usually occurs between __ and __ years.
(What is average age in U.S.?)
11-14 y/o
- Avg age in U.S. is 12.5 years
No pubertal development by age __ warrants investigation.
13
In terms of Tanner stage differences, what is generally considered abnormal?
A greater than 2 stage difference
What’s the first sign of pubertal development in males?
Increase testicular size (over 3mL)
What’s the first sign of pubertal development in females?
Breast buds (thelarche)
Puberty is considered ‘precocious’ if before age __ in males, __ in females.
9 (males)
6 (females, but 6-7 could be abnormal as well)
Discuss the 5 stages of Tanner female breast development.
- Child’s typical appearance
- Increasing growth
- Increasing growth
- Nipple forms *secondary mound
- Adult (areola on plane w/rest of breast tissue)
Discuss the 5 stages of Tanner female pubic hair development.
How is it different in the male?
- No hair
- Peach fuzz
- *Coarse hair
- Growth
- More growth
- Basically the same for male and female stages
Discuss the 5 stages of Tanner male testicle and penis development.
- Tiny (typical child)
- *Over 3mL volume (first sign of puberty in males)
- Growth
- More growth
- Adult size
