Pregnancy - Montemayor Flashcards
How is pregnancy duration determined?
Date of last mestrual period (LMP)
What is the mean duration of pregnancy?
40 weeks total (gestational age)
Or
38 weeks from ovulation - (embryonic/fetal age)
When do HCG levels begin to rise after ovulation of a fertilized egg?
8 Days
What secretes HCG?
The trophoblast
What are the four major hormones of pregnancy?
- HCG
- Progesterone
- Estrogens
- Human Placental LActogen (hPl)/Human chorionic omatomammotropin (hCs)
What are the three types of estrogens to be aware of?
Estrodiol
Estrone
Estriol
Identify which line corresponds with what hormone.
In the first trimester, hCG rescues the corpus luteum to stimulate luteal estrogen and progesterone production. What takes over hormone synthesis from the corpus luteum?
The placenta
What subunit of hCG is detected by pregnancy tests?
Beta subunit. (beta-hCG)
What is responsible for morning sickness?
hCG
When does hCG peak?
~10 weeks of gestation.
What hormones is the structure of hCG similar to? Which is it most similar to?
LH, FSH, TSH
Most similar to LH
hCG binds to what receptor with high affinity?
LH receptors
What is the primary action of hCG?
Stimulates LH receptors on corpus luteum…
- Prevents luteolysis
- Maintains high luteal-derived progesterone production before the placenta takes over (1st 10 wks.)
What are the other actions of hCG?
–Weakly binds TSH receptors
•Transient gestational hyperthyroidism
–Stimulates fetal Leydig cells –> Testosterone
–Stimulates fetal adrenal cortex
When does the luteal-placental shift take place?
~8-10 weeks
What is the function of progesterone with regard to pregnancy?
•Absolutely required to maintain a pregnant uterus
–Quiescent myometrium
How is progesterone production an indicator of fetal health?
It isn’t, progesterone production is independent of fetus
High levels of progesterone production continues with the availability of?
•CYP11A1, and 3β-hydroxysteroid dehydrogenase (3β-HSD), and **maternal cholesterol **
What are the major actions of progesterone in pregnancy?
–↓ uterine motility/contractions
–↑secretory activity necessary for nouishment, growth, and implantation of the embryo
–↑ fat deposition early in pregnancy
•Stimulates appetite, diverts energy stores from sugar to fat
The placenta takes of luteal-production of estrogens, what does it need from the fetal adrenal gland?
Needs 19-carbon androgen (DHEA-S)
What is the feto-placental unit responsible for the production of?
–Estradiol-17β
–Estrone
–Estriol (major estrogen of pregnancy)
Can you use estrogen as an indicator of fetal health?
Yes, since its production depends on a healthy fetus
We discussed seven effects of estrogen in pregnancy, list as many as you can.
- –↑ Uteroplacental blood flow
- –↑ Uterine smooth muscle hypertrophy (mitogenic effect)
- –↑ LDL receptor expression on syncytiotrophoblasts
- –↑ Prostaglandins
- –↑ Oxytocin receptors
- –↑ Mammary gland growth
- –↑ Prolactin secretion (maternal pituitary)
The estrogen:progesterone ratio shifts late in pregnancy, why?
To prepare for parturition
What does the drop in estrogens and progesterone after parturition allow for?
•PRL action on the breast and lactation
Human placental lactogen (hPL) is also known as?
•Human chorionic somatomammotropin (hCS)
What produces hPL/hCS?
syncytiotrophoblasts
What are the levels of hPL proportional to?
Placental growth
What is the main action of hPL?
•↑ glucose availability for the fetus
–Inhibits maternal glucose uptake
–Lypolytic action –> shift maternal energy use to FFAs
What else does hPL do besides its antagonism of insulin activity?
•Simulates mammary gland development
What are some things that can cross the placental barrier? (mother to fetus)
- O2
- water
- electrolytes
- carbs, lipids, a.a., vitamins
- hormones (some)
- antibodies
- drugs (some)
- Viruses (most)
Syncytiotrophoblasts produce what classes of hormones?
Steroid and peptide hormones
Name five functions of the placenta
- Maintain pregnant state of the uterus
- Stimulate lobuloalveolar growth and function of maternal breasts
- Adapt aspects of maternal metabolism and physiology to support fetal growth
- Regulate aspects of fetal development
- Regulate the timing and progression of parturition
Identify the hormones shown on the graph.
What are two major limitations of the placenta?
- Cannot make adequate cholesterol
- Lacks enzymes required for complete biosynthetic pathway for estrone, estradiol, and estriol production.
Identify the blocked out items
What are the changes to the pituitary during pregnancy?
- ↑ Pituitary size x 2
- ↑ Prolactin (PRL)
- ↓ LH and FSH production
- ADH secretion augmented
What can happen due to the increased pituitary size in pregnancy?
–If compressed against optic chiasm, enlarged pituitary can cause dizziness and vision problems
–Can be susceptible to vascular insult and necrosis – Sheehan’s syndrome
What does the increased prolactin during pregnancy lead to?
–Estrogen promotes PRL release from anterior pituitary
–Lactotroph hypertrophy and hyperplasia
What causes the decreased LH and FSH production during pregnancy?
–Negative feedback inhibition of estrogens + progesterone
In what way is ADH secretion augmented during pregnancy?
–Threshold altered by progesterone action
–ADH released at lower osmolality (lower “set point”)
What happens to the thyroid during pregnancy?
•↑ Thyroid size
•hCG weakly binds TSH receptors
–Transient gestational hyperthyroidism
•↑ Total T4 and Total T3 (2x)
–Estrogen promotes increased liver production of thyroxine-binding globulin (TBG)
–No change in Free T4 and Free T3
What adrenal changes occur during pregnancy?
- ↑ Cortisol
- ↑ Aldosterone (~ 8-10 x)
What does placental 11β-dehydrogenase type 2 do?
Inactivates cortisol to protect the fetus
How is aldosterone upregulated in pregnancy? Do we get hypernatremia, hypokalemia, hypertension? What blunts the action of aldosterone?
–Estrogens stimulate ↑ liver production of angiotensinogen and renal renin production
•↑ ANG II and Aldosterone
–Does not result in hypernatremia, hypokalemia, or hypertension
–Progesterone blunts aldosterone action (competes for mineralocorticoid receptors)
What are the four major cardiovascular changes in pregnancy?
- ↑ Blood volume
- ↑ Cardiac Output
- ↓ TPR
- ↓ MAP (or remains close to normal)
What happens to hematocrit during pregnancy?
Drops
What happens to HR and SV during pregnancy?
Increase
↑ blood volume ~45% near end of pregnancy (75-100% for twins, triplets). What are two reasons for this?
- Facilitates adequate fetal perfusion & exchange of nutrients/wastes
- Protects mother from blood loss during delivery
What is the main factor contributing to the increased in blood volume?
↑ plasma volume (~ 50%)
What causes the increased plasma volume during pregnancy?
•↑ NaCl retention
–↑ Aldosterone
–Estrogen stimulates ↑ angiotensinogen (liver) & renin (renal) production à angiotensin II & aldosterone
•↑ H2O retention and intake
–Lower threshold for ADH/AVP and thirst during pregnancy (overall ↓ osmolality)
–Increased sensitivity of osmoreceptors
Why does hematocrit drop during pregnancy?
–↑ RBC production rate doesn’t match ↑ plasma expansion
How is cardiac work minimized as CO increases?
•↓ Viscosity: ↓ TPR
To what degree does CO increase during pregnancy?
•↑ 30 – 50% by end of pregnancy (~ 35% ↑ in 1st trimester)
How much does HR increase in pregnancy?
15-20 bpm
What happens to SV in very late pregnancy?
–SV may periodically decrease due to compression of the IVC
–↓ VR –> ↓ EDV –> ↓ SV
(positional changes)
Where does the increased CO distribute to?
–Uterus: 15% of CO (~ 1% normally)
–Renal: ↑ by 40%
•Elimination of additional wastes
–Skin: temperature regulation
–Heart: support increased CO
–Breasts: mammary development
What percent increase in CO do the brain, gut and skeleton recieve?
0%
What two factors result in decreased TPR/SVR during pregnancy?
- Additional, low-resistance circuit: utero/placental circulation
–Vasculogenesis and angiogenesis
- Vasodilation
What promotes the vasodilation seen in pregnancy>
–Estrogen & progesterone: proposed antagonists to vasopressive action (ANGII)
–Progesterone may promote vasodilation as a smooth m. relaxant
What are the changes to starling forces in pregnancy?
- ↑ capillary hydrostatic pressure
- ↓ capillary colloid osmotic pressure
What causes the ↑ capillary hydrostatic pressure?
–↑ venous pressure in L.E. due to:
•Compression of IVC by growing uterus
•Increased venodilation under hormonal influence
What causes the ↓ capillary colloid osmotic pressure during pregnancy?
–Maternal synthesis of plasma proteins does not keep pace with increase in plasma volume
What are the three primary respiratory changes seen during pregnancy?
- Elevation of diaphragm
- ↑ O2 demand and CO2 production
- ↑ Sensitivity to CO2
What causes the elevation of the diaphragm during pregnancy?
- Increased intra-abdominal pressure with fetal growth
- Progesterone effect: relaxing m. and fascia
- ↓ RV and ↓ FRC
What causes the ↑ O2 demand and CO2 production during pregnancy?
- Support of fetal metabolism and pregnancy
- ↑ O2 consumption (~20%)
What causes the ↑ Sensitivity to CO2 during pregnancy?
- Progesterone effect (estrogen)
- ↓ Medullary respiratory center set-point for respiratory response to central chemoreceptor detection of CO2
- ↑ TV and Alveolar Ventilation
- ↓ Pco2 (From ~ 40 à 32 mmHg)
How do these values change due to pregnancy?
- Functional residual capacity (FRC)
- Residual volume (RV)
- Tidal volume (TV), ↑ minute ventilation
- Alveolar ventilation (VA)
- Respiratory rate
- Pco2
- ↓ Functional residual capacity (FRC)
- ↓ Residual volume (RV)
- ↑ Tidal volume (TV), ↑ minute ventilation
- ↑ Alveolar ventilation (VA)
- Respiratory rate ~ unchanged (RR)
- ↓ Pco2
The net result of respiratory changes during pregnancy leads to
↑ ventilation –> ↓ Pco2
causing what?
- Respiratory alkalosis
- Renal compensation: ↑ HCO3- excretion
Describe the affinity of fetal Hb for O2 and CO2 relative to maternal hB.
- ↑ Fetal Hb O2 binding affinity (> maternal)
- ↓ CO2 affinity, favoring pick-up by maternal blood
What are 5 major changes in renal function during pregnancy?
- ↑ RBF and ↑ GFR (~ 50%+)
- ↑ Plasma renin, angiotensin II, and aldosterone
- ↑ Na+ retention
- ↑ H2O retention and intake
- ↓ Serum Na+ (~ 5 mEq/L decrease)
What causes the increased RBF and GFR?
–↑ blood volume and CO
What causes the ↑ Plasma renin, angiotensin II, and aldosterone?
–Estrogens stimulate increased production
What causes the decreased serum Na+?
–Change in set-point for ADH/AVP and osmoreceptor sensitivity
What causes the ↑ Na+ retention during pregnancy?
–↑ Aldosterone
What causes the ↑ H2O retention and intake?
–↓ threshold for ADH/AVP & thirst during pregnancy
–Increased sensitivity of osmoreceptors Net: ↓ osmolality despite ↑ Na+ retention)
What are four major changes to the GI system that occur during pregnancy?
- ↓ Gastric emptying rate (progesterone)
- ↓ LES tone (progesterone)
- ↑ Intra-abdominal pressure
- ↓ Intestinal motility
What causes the constipation seen in pregnancy?
•↓ Intestinal motility
What are three key components of maternal nutrition?
Protein
Folate
Iron
What does protein do for the mother and fetus? How much does one need?
–Supports fetus, placenta, uterus, breasts, blood volume
–Additional 30 g protein/day
What does iron do for the mother and fetus? How much does one need?
–Supports increased maternal Hb, placenta, fetus
–7 mg/day absorbed iron requirement (vs. 1.5 mg/day nonpregnant)
–60 mg/day supplement recommended
What does folate do for the mother and fetus? How much does one need?
–Supports increased RBC production; protects against neural tube defects
–400-800 mg/day folic acid supplementation recommended
What causes the myometrial quiescence during pregnancy?
–Progesterone
–Relaxin
When does onset of labor usually occur?
What initiates it?
How is it sustained?
–38 wks. following fertilization (fetal age)
•40 wks. after last menstrual period (gestational age)
–Initiated by hormonal (endocrine, paracrine) and mechanical factors
•Process not completely understood
–Positive feedback mechanisms sustain
What are braxton hicks contractions? When do they peak?
–Periodic episodes of weak, slow rhythmic contractions during pregnancy
–Become very strong during the last hours of pregnancy
Braxton Hicks Contractions eventually become labor contractions. What goes down now?
–Stretching the cervix
–Push baby through the birth canal
What is false labor?
•contractions initially become stronger but then fade away
– Failure to re-excite uterus with subsequent positive-feedback mechanism
•Afferent pain signals from uterine contractions reflexively result in?
abdominal m. contraction
What are the three stages of labor?
- Cervical Dilation and Effacement
- Descent and Expulsion
- Expulsion of the Placenta
Cervical Dilation and Effacement is stage one, this initates labor, how do contractions change? What is the average time spent in this stage?
- Contractions go from ~ 30 min to <10 min. apart
- Average 7-12 hrs. (1st pregnancy range: 8-24 hrs.)
Descent and Expulsion is the second stage and the point of active labor. The cervix is fully dilated here. What happens with the contractions? How long does this normally take?
- Contractions push fetus downward; delivery
- Average 20-50 min. (Longer for 1st pregnancy vs. after many)
Expulsion of the Placenta sees the uterus contract reducing area of attachment. What does this result in? How long does it take>
•Separation of placenta results in bleeding and clotting
–Bleeding limited by uterine contractions that compress vessels supplying placenta
•Average 15 min. (Range 10 - 45 mins.)
What are the two prostaglandins we care about here?
•PGF2α and PGE2
You should probably draw this. She spent some good time on this.
What is believed to initiate labor?
Prostaglandins
What do prostaglandins do to the Uterus?
•↑ uterine smooth m. contractility
What are the three main actions of prostaglandins?
- Stimulate myometrial smooth m. contraction
- Promotes gap junction formation between uterine smooth m. cells
- Softening, dilatation, and thinning (effacement) of the cervix
In addition to prostaglandins, what hormone promotes gap junction formation?
Estradiol
What can large doses of prostaglandins be used for?
Inducing labor (typically small doses gradually administered)
What impact does aspirin have on labor? How?
•Aspirin: inhibits labor and prolongs gestation
–Reduces PGF2α and PGE2 formation
What are the four roles of estrogens during parturition?
- –↑ Gap junctions
- –↑ Oxytocin receptor expression
- –↑ Myometrial sensitivity to oxytocin
- –↑ Prostaglandin production
Identify the hormones indicated.
What impact does oxytocin have on labor?
maintains it
What is the primary stimulus for oxytocin release?
•Distention of cervix
Oxytocin is released by the posterior pituitary, what is this reflex called? What is the response to? How does release changed during the labor stages?
–Neurogenic reflex (Ferguson)
–Response to stretching of the cervix
–Bursts of oxytocin are released during Labor Stage 1; frequency increases with progression of labor
What impact does increased estrogen have on oxytocin receptors?
•Estrogen increases number of oxytocin receptors
What does oxytocin receptor activation do to uterine smooth muscle?
Contracts it
•PLC –> IP3 –> ↑ [Ca2+]i –> activate calmodulin –> MLC kinase à phosphorylation of regulatory light chain à smooth m. contraction
What are uterine contractions important for after delivery of the placenta?
- constricting blood vessels after placental delivery
- Promotes hemostasis
What are the three actions of Placental Corticotropin-Releasing Hormone (CRH)?
•Production and maternal serum levels rise quickly late in pregnancy/labor
–↓↓ CRH-binding protein
–↑ Free CRH•Sensitizes uterus to prostaglandin & oxytocin•Stimulates fetal ACTH
–↑ fetal adrenal cortisol (positive feedback for CRH)
–↑ fetoplacental estrogens
What is relaxin produced by?
What does it do during labor?
When does its production ramp up?
- Produced by corpus luteum and placenta
- Thought to promote myometrial quiescence during pregnancy
•Production increases during labor
–May soften cervix during labor
What does the fetal pituitary produce?
Oxytocin
The fetal adrenal gland produces cortisol (+CRH), what does this do?
–Fetal cortisol induces surfactant production in the lungs at about 32 weeks (range 24-35 weeks)
What does the fetal placental membrane do?
produces prostaglandins
What are the Fetal & placental signals preparing for/initiating labor?
–CRH production by the placenta
•↑ fetal pituitary production of ACTH
•↑ fetal adrenal production of cortisol and DHEAS
•↑ fetoplacental estrogen production
–Cortisol: positive feedback to ↑ placental CRH production
–
–CRH promotes contractions by sensitizing uterus to prostaglandins and oxytocin
–Estrogens also stimulate contractions
What mechanical factors increase uterine contractility?
- Stretch of smooth m. –> Increases smooth m. contraction
- Contractions stimulate uterine prostaglandin production
- Ferguson Reflex: Uterine contractions push baby against cervix à stretching cervix à stimulating more oxytocin
