Female Reproduction Flashcards
(137 cards)
1
Q
Amenorrhea
A
Complete lack of a period. This is also a marker of pregnancy!!!!!!!! Doesn’t matter if patient is 40. Age alone is not enough to diagnose menopause.
2
Q
Oligomenorrhea
A
Irregular, random periods
3
Q
G0P0 would suggest
A
primary issue. Note that the G means that she is carrying a child
4
Q
G1P1 would suggest
A
secondary issue. Note that the P1 means she gave a LIVE birth.
5
Q
Perimenopausal
A
Transition period to menopause. Expect hot flushes and unpredictable periods
6
Q
Presentation of menopausal women.
A
Night sweats
hot flushes
Diagnos patient with a metabolic panel. Ultrasound wouldn’t help here, can be used.
7
Q
Describe follicular phase
A
Follicular (ovarian perspective): PROLIFERATIVE phase (uterine perspective). days 1-14. Menses (period…vaginal bleed) occurs right in the BEGINNING! Within days 1-4/ FSH is increasing, granulose cells proliferate and E2 is secreted. Later, the dominant follicle is selected from the growing cohort. E2 is still increasing. Finally, Remainder of the cohort undergoes atresia (death). Ovulation occurs on day 14.
8
Q
Describe luteal (secretary) phase
A
Days 15-28. Focuses more on the uterus.
9
Q
Describe the Graafian/preovulator/selected follicle
A
- Teca cells on the outermost shell. Has LH receptors. Makes P4, Androtenedione, and T.
- Granulosa cells are second layer in. Has FSH R. makes E1, E2-17B, and Proesterone.
- Antrum: Follicular fluid filled with a ton of hormones
- Oocyte. the actual egg. The most inward.
10
Q
What is job of GnRH? Think hypothalmic-pit-ovarian-adrenal axis. What happens to the storoids produced by the follicular cells?
A
Secretes LH and FSH. Note that granulos cells express both FSH and LH receptors. Theca cells only express LH receptors. Also note that the produced steroids act as negative feedback, killing off GnRH, and thus stopping FSH and LH secretion.
11
Q
Job of CYP17
A
makes androens: androstenedione and T.
12
Q
Job of CYP19, aromatase
A
estrogens: makes E1, E2-17B (important for bone)
13
Q
Job of CYP11A
A
progestins: prenenolone (P5) and progesterone (P4)
14
Q
What is the involvement of steroid sulfatase?
A
Think DHEAS, which is secreted from the adrenal cortx. S = sulfate. TO turn into DHEA, you need a desulfatase, which is what this it.
15
Q
What is the pattern of folliculogenensis. Detail the hormone genesis.
A
Primordial-primary-preantral-preovulatory-corpus luteum
Story: Nothing is secreted in primordial cells. Period. It is not until primary and preantral development that anything is made. At this point, Thecca cells make more androstenedione and granulosa cells make more E2. Leaving the preantral stage, Thecca stells increases androsteindione and granulosa cells secrete more E2….a bunch more. At preovulatory stage, Thecca cells are makeing a crap ton of androsteindion, and E2 in granulose calls is dumb high. At corpus luteal stage, Adrosteonodione has a sligth drop in production, and up until now progesterone was barely being made. Now, P4 is Sky high. In the case of the granulaose cells, E2 also took a hit inproduciton, but it still a lot. progesterone was also weak up till this point. Now, it is the highest hormone being made, period, ever. Like, beyond dumb high.
16
Q
Why does P4 get sky high in the corpus luteum stage?
A
Primes urterus to accept egg. This is day 14.
17
Q
Describe the general signaling pathway for androgen production on a thecca cell.
A
LH binds to LH receptor. This causes LDL to drop cholesterol into the cell. The cholesterol passes through StAR protein, and enters the mitochondria innermembrane. Cholesterol is then converted to PREGNENOLONE (P5) via CYP11A (rate limiting step!!!!!!!!). This is a WEAK progesterone. You cannot skip this step. It is only after P5 escapes the mitochondria that it meets 2 enzymes. When passing CYP17, it makes DHEA. When Passing 3b-HSD, it makes PROGESTERONE. Progesterone is then converted further with CYP17 to make androstenedione. Some of this androstenedione runs through 17B-HSD to become T. T and Androstenedione (way more A than T! Like, no competition). BOTH leave the thecca cell. Note that DHEA can be converts to androstenedione with 3B-HSD.
18
Q
Describe the general signaling pathway for androgen production on a granulosa cell.
A
FSH binds to FSH receptor. This causes LDL to drop cholesterol into the cell. The cholesterol passes through StAR protein, and enters the mitochondria innermembrane. Cholesterol is then converted to PREGNENOLONE (P5) via CYP11A (rate limiting step!!!!!!!!). This is a WEAK progesterone. You cannot skip this step. Although pregennelone is made, this is not the important part. What is important is that the binding of the FSH tot eh receptor caused the chain tha tled to steroid horomone expression. This allows for the androstenedione and T that were made from the thecca cells to actually enter the granulosa cells. The granulosa cells then tale the androstenedione, convert it with cyp19 to make E1. The T s converted with the same CYP19 to make E2. E1 and E2 are rleeased as E2. Both E1 and E2 are released, but WAAAAY more E2 is released than E1.
19
Q
What is a corpus luteum?
A
It is the remains of the ovulation of the egg. Upon follicle bursting and egg release, the thecca and granulosa cells are left. This is a terminal differentiated state. The granulosa and thecca cells are now titled grulosa lutein and thecca lutein cells.
20
Q
What is the new job to the granulosa LUTEIN cells (that are now the corpus luteum?)
A
LH binds to LH receptor. Yes, THE GRANULOSA CELLS NOW HAVE LH RECEPTORS, in addition to the FSH receptors they always had. This causes LDL to drop cholesterol into the cell. The cholesterol passes through StAR protein, and enters the mitochondria innermembrane. Cholesterol is then converted to PREGNENOLONE (P5) via CYP11A (rate limiting step!!!!!!!!). This is a WEAK progesterone. You cannot skip this step. When P5 leaves the mitochondria, it is converted with 3B-HSD to make a BUNCH of progesterone. There is still E2 remaining from thecal androgens tho. Both Progesteone and E2 are released, but Progesterone is released in LARGER quantities…E2 is still being produced in a solid amount tho. Note that the combo of Progesterone and E2 are released to prepare the uterus fro implantation.
21
Q
What kind of cell signaling is involved in the hormone productions of the ovaries?
A
cAMP-PKA and pPKA.
22
Q
What are the 5 families of steroid hormones?
A
glucocorticoid, mineralcorticoids, androgens (T), estrogens, progestines
23
Q
What hormone presence could screw up GnRH? What is common between cushings syndrome fertility?
A
- Prolactin
2. These guys are all infertile.
24
Q
T or F: The recruitment of cohort of follicles depends on LH or FSH
A
HARD FALSE. That releases is controlled by the ovaries intrinsically. All of the growth and development that occurs AFTER recruitment depends on FSH and LH.
25
How many months does it take for a cohort to finish and select the chosen one follicle?
3-4 months. Note the cascade effect. Each month, a new cohort is selected.
26
Why do you need all of these growing follicles present at different stages?
In order to support the entire process, since each one of the follicles in their respective cohorts are secreting growth hormones and such, which effect all of the present cohorts in a paracrine manner.
27
When is FSH and LH needed for follicular growth?
Transition from primary to secondary follicle size and beyond. Note that during this process, random follicles go through atresia (die off). More than 98% of all growing follicles die.
28
Describe the hormonal control of folliculogenesis
1. Primordial to primary...intraovarian growth factors. NO FSH or LH present.
2. Secondary and beyond...growth factors are numerous, cytokines are numerous, FSHS AND LH ARE SQUAD DEEEP. Steroid hormones come thru too.
3. Oocyte matures
4. Growth/steroidogenic differentiation of granulosa and thecca cells
5. Angiogenesis, allows fro ovulation of fertilizable oocyte.
29
What controls the hormonal events during the luteal phase of the cycle?
Corpus luteum
30
Prior to the preovulatory surge, what are the TWO reasons FSH stays so low? Where is the estrogen coming from?
1. E2 is still causing that negative feedback at the level of the GnRH pulse gen, so FSH is not being released enough
2. Granulosa cells are secreting Inhibin B, which stops FSH secretion
Note that the estrogen is coming from the Graafian follicle.
31
What cause the negative feedback of E2 to switch to positive feedback (referring to before ovulation). What happens to Inhibin B?
A sudden increase in E2 production. This causes pulse generator of GnRH to change firing pattern, leading to the increased release of FSH. Note that the gonadotropes secrete FSH and LH. In this particular case, the gonadotropes start to secrete Activin (inhibin B is cut out). It acts in an autocrine manner, turning around and telling the gonandotropes to secrete FSH.
32
What happens post-ovulation? What happens to the granulosa cells?
P4 and E2 are produced like no other from the corpus luteum. P4 and E2 in it of itself is likely enough to kill off FSH production (remember, the negative feedback...contraceptive concept). In terms of the granulosa cells in the corpus luteum, they are now granulosa lutein cells. These guys no longer secrete Inhibin B. They secrete Inhibin A. Inhibin A, just like Inhibin B, knocks down FSH secretion at the level of the ant pit.
33
Why does FSH have to keep changing the way it does during the menstrual cycle?
When FSH is low, follicle growth and differentiation is at a bare minimum. So a lot of the follicles die at the the early and later days. They are too small, and have less FSH receptor, so they can't grab onto the small amounts of FSH.
34
What causes granulosa cellls prior to ovulation to develop LH receptors, in addition to the FSH receptos it already had? What does LH cause graulosa cells to do?
The increase in FSH (caused by the increases in E2, remember?). Note that this happens because the follicle is getting ready to become the corpus LUTEUM. It also causes the granulosa cells to produce Inhibin A, which was already established to reduce FSH in the granulosa luteal cells of the corpus luteum. Note that ovulation has not yet occurred. It is about to tho.
35
What horomon is absolutely necessary for follicle growth?
FSH
36
What is the difference in pattern of secretion of LH from FSH?
There is none.Same exact pattern. Same negtaive and positive feedbacks caused by steady and then an increase in E2. Same ovulatory surge. The same increase in P2 and E2 from corpus luteum still causes FSH to decline again due to negative feedback. You still have Inhibin B and then Inhibin A from the respective granulosa cells.
37
Describe the pattern of estrogen production throughout the cycle.
E2 levels are relatively low until they gradually increase closer to the date of ovulation (peak is preovulatory). It peaks out right about the time of ovulation. Note that E2 stays relatively high through the mid luteal phase, and then starts to decrease. Note that the main source of E2 is still from the preovulatory follicle.
38
Describe the pattern of progesterone production throughout the cycle.
Stay dumb low through most of the follicular phase of the cycle. THere's then a preovulatory "blip" of P4 caused by the fact that the preovulatory follicle is starting to become a corpus luteum. Skyrockets in the luteal phase as soon as ovulation occurs. Peak levels are also mid-luteal, just like E2.
39
Where is most of the E2 coming from in the follicular stage? Progesterone in the follicular phase? Where are most of the steroid hormones come from in the luteal phase of the cycle?
1. Preovulatory follicle. Note that the other follicles present are contributing.
2. Preovulatory follicle
3. Corpus luteum
40
What is associated with the increase in progesterone production?
Rise in body temp. Note that progesterone is a thermogenic hormone.
41
Describe how progesterone can be used to determine pregnancy.
Increase in body temp (BBT) only happens is increase in P4, if corpus luteum is formed, if ovulation occured, if there was an LH surge at ovulation day 14, if there was E2 feedback (positive and negative), if there was a health dominant follicle with supporting follicles, if FSH/LH secretion was A1, if neruoendocrine function was normal. If you knock out one of these, there is no increase in body temp?
42
What is the first test you do on a woman that comes in suspecting infertility issues?
hCG test. Note that if patient is in amenorreia, they could very well be pregnant. You can't have a cycle if you have a baby growing in you.. Do this after you checked the body temp and ruled out paternal issues.
43
How does progesterone during luteal phase affect the hypothalamus? Where is the progesterone coming from? Why is this all important?
Progesteone from corpus luteum at sustained, elevated levels, increases progesterone receptors in the hypothalamus. This leads to a decrease in GnRH pulse frequency, which decreases FSH and HEAVILY decreases LH production. Note that the placenta also makes progesterone, and this too will cause the same effect. Also note that progesterone contraceptives work the same way too, elevating P4 and increasing progesterone receptors, decreasing the GnRH pulse freq. Please remember that without the gonadotropins of LH and FSH, you CANNOT ovulate. Goes back to the whole follicular development. You need both for the follicles to continue to grow and differentiate.
44
How does estrogen affect the GnRH pulse generator? What makes this so brutal? How does T affect GnRH pulse freq? Where is T coming from? If T is not coming from the leydig cells, where could it be coming from?
E2 from the granulosa cells of the dominant follicle binde to ER-alpha in the GnRH pulse generator. This causes a decrease in the GnRH puls freq, which heavily cuts down FSH, but also cuts down LH. Remember that P4 cuts down the opposite, cutting down LH more than it cuts down FSH. Just remember that FSH and E2 are from the same granulosa cells. Blocking FSH more brutally kills follicle development. Follicles would be even more likely to reach the preovulatory stage without FSH. Leydig cells can also screw up FSH anf LH production through a similar mech. They crease T, which is converted to E2 with CYP19. E2 then bindes to ER-alpha and does the dame damage described above. Note that this process could just as easily happen in patients with an condition of HYPERandrogenemia such as PCOS (these guys can't cycle. too much T, so too much E2, so this described pathway keeps occuring) and anabolic androgen abuse (same deal).
45
What happens at the end the cycle? (days leading up to d28)
Endometrium sheds and menstrual bleed occurs, feeding into the next follicular phase.
46
Describe thw difference between luteal phase defects and follicular phase deffects.
Luteal phase defects: screws with mechs needed to implant egg and cause pregnancy, as well as feedback needed to start next cycle.
Follicular phase defect: disrupts folliculogenesis, oocyte maturation, and most certainly adversely affects ovulation.
47
Describe the dominant follicle before and after the gonadotropin surge at d14.
Before: High E2. In early luteogenesis, tehre's an onset of P4 to prime the uterus.
After surge: High P4 and E2 which supports the endometrium. The P4 is specifically there to relax and quiet the corpus luteum.
48
Describe the changes in the endometrium at the beginning and end of the follicular/proliferative stage
Beginning (days 1-4): There is a lot of angiogenesis repair because of the shedding of the endometrium prior.
End: There is a rise in E2 (from follicle), which triggers progeserone receptor, estrogen receptor, growth factors, and ultimately the proliferation and angiogenesis.
49
Describe the changes in the endometrium throughout the secretary/luteal stage.
Early in luteal phase, the P4 and E2 high levels promote angiogenesis. Mid way in the luteral phase, P4 lowers presence of P4 and E2 receptors. Reason: preparing endometrium to shed. THe suddon drop in E2 and P4 support (late luteal phase) leads to the period bleed. This withdrawl causes shedding of endometrium. Note that without P4 and E2, the endometrium does not have the support it needs to function.
50
What is REI? ART
REI: reproductive endocrinology and infertility (fellowship, subspecialty)
ART: Assisted reproductive technologies
51
Job of FSH
Stimulates ollicle growth and differntiation. More FSH - more follicle growth and differentiation.
52
Job of LH
Triggers final phase of maturation of selected follicle and ovulation
53
Job of E2 and P4
prepare receptive uterus for implantation
54
Describe the Clomiphene protocol goal and mech
Goal: promote endogenous FSH by blocking negative feedback
Mech: Remember: E2 is the specific hormone responsible for FSH negative feedback. So, you give an ER-alpha ANTAGONIST. This prevents E2 from binding to the hypothalamus and messin up the GnRH pulsatile setup. So, FSH runs free, and you get way more follicle stimulation. When this is done, you'll see series of GnRH spikes, and FSH will be super stimulated, leading tot the maturation of SEVERAL (not one) preovulatory follicles. Track their growth via ultrasound to prevent maternal death. At intened ovulation date, you aspirate the eggs, conduct invertro fertilization during mid luteal phase, the n add P4 support into first trimester. The P4 is used to quiet and stabilize her uterus.
55
Describe the exogenous gonadotropin protocol goal and mech
Goal: Desensitize her hyperthalmic receptors so that you take over her hormonal control
Mech: If you give a high enough dose of EITHER an agonist or antagonist of GnRH, you WILL ablate the GnRH pulse generator. This BLOCK FSH secretion. Humans step in and admin exogenous gonadotropin. This means, we must give BOTH FSH and LH, but instead of LH, we use hCG (which is better....higher binding affinity). After the, the story is exactly the same as in the clomiphene protocol.
56
What hormone promotes endometrial thickening? Which one keeps it from shedding?
1. E2
| 2. P4
57
What happens if woman with amenorrhea is making E2 and you give them P4 for 7-10 days, then stop the P4?
Woman will have period since endometrium would no longer be stable. Mimics luteal phase physiology. Remember, E2 causes endometrial thickening.
58
What happens if woman with amenorrhea is NOT making E2 and you give them P4 for 7-10 days, then stop the P4?
She should NOT have withdrawal bleed. However, if you give E2 + P4 for 21 days, then stop, there should be a withdrawl bleed. This mimics menstrual cycle.
59
What is somethign you would expect in a woman with an E2 receptor blockage or something related? What would happen in the case of a woman making too much T?
1. Osteoporosis
2. Premature closure of epiphyseal plates, leading to short stature
3. Too much T would lead to severe facial acne, voice change, dislipidemia
60
When can fertilization occur to lead to conception? Assuming successful fertilization, when would implantation occur? WHen does hCG start being produced?
Within 48 hours AFTER ovulation. If you overshoot this time, you missed your shot. Implantation would then occur between days 20-24 in luteal phase. hCG is produced after implandation.
61
Why is days 20-24 the best time for implantation?
E2 and P4 are maxed out. It's as ready as its ever going to be However, the window of implantation is usually were the ambiguity occurs.
62
What are the trimester weeks?
1-12 (1st)
13-26 (2nd)
27-39 (3rd)
39-42 (delivery)
63
WHat happens in trimetster 1
Maternal recognition of pregnancy. Growing conceptus starts producing hCG. GnRH is being secreted from the PLACENTA, not the hypothalamus. GnRH targets trophoblasts, which causes it to secrete human chorionic gonadotropin (hCG). hCG targets corpus luteum (ealry first trimester), which makes even more P4 than she made in luteal phase. The P4 straight up acts as negative feedback to pituitary, cutting off hypothalamus control. THis setup takes a month to occur.
64
What is the bady doing in the first trimester?
ACTH is targeting fetal adrenal gland, which is making DHEAS and Cortisol (essential for development of fetal organs). Maternal P4 is sent directly to the kiddie, who will convert it into more DHEAS and cortisol. Placenta later takes DHEAS, removes the S with steroid sulfatase, and converts it to E3 in the woman.
65
When does hCG lose importance? WHen does luteral phase switch to that of control by the placenta?
When the negative feedback turns off the pit. Remember that it targets the corpus luteum, which then spikes P4 production. Switching from human to placenta occurs at week 10 about. hCG stays low after. Note that all of the hormones dip after this.
66
Describe presence of E2 and E3 during the luteal steroidogenesis to placental/fetal adrenal steroidogenesis periods. What is the benfit of having the estrogens overshoot eachother?
E2 and E3 are steadily increasing together, stay about the same amount as each other, up until the end of the 2nd trimester. E2 levels plateau soon after, while E3 skyrockets....10:1 increase ratio of E3:E2. Note that up until the end of the 3rd trimester, E3 and E2 were competing against each other, making it hard for either to bind.When E3 skyrockets, this problem is eliminated. Note that E3 leads to activation of uterine estrogen receptor, which helps with pregnancy.
67
WHat happens to the mother during weeks 1-12?
1. Increase in intravascular volume
2. RBC mass increases 30% due to progesterone. With regard to pregnancy, and you are in panic, name progesterone.
3. She is vasodilated relative to normal. Reason: P4. This leads to high perfusion (Q) and low pressure (P). Goal is to increase CO to better perfuse placenta
68
What happens tot he woman during second and third trimester?
Maternal HR increases by about 10 bpm. This leads to a 40% increase in CO. SO the increase is mainly attributed to HR, not SV. Goal is still to supply placenta, which supplies the baby.
69
CO equation
HR x SV
70
The increase plasma volume, leads to increased venous pressure. But, her central venous pressure (RAP) is unchanged, WHY?
HR increased, WHICH INCREASED HER CO (the CO part is the correct response). This is the compensation to get rid of the newflow of blood into the RA.
71
Why is pulm resistance reduced and yet pulm artery P unchanged?
Increased CO (because of her increased HR, remember?)
72
What do you expect to see in patient who is carrying placenta?
1. Increase in Pmcf
2. Increase in CO
3. DECREASE in TPR (due to dilation, caused by progesterone)
4. Increase in inotropy (he did not talk about this, but it's on the graph. Not as important)
73
How does RAAS get involved during pregnancy?
1, Placenta is still making a ton of E2, which Directly increases RAS stimulation (you need to know this). Also note that BECAUSE THE PLACENTA IS TAKING SOOO MUCH BLOOD AWAY FROM THE MOM, there is a perceived vascular underfilling (dilatory effects pf P4 reduced peripheral resistance, and the placenta is acting effectively as a shunt).
2. RAAS is stimulated, and AII is ultimately made.
3. AII calls Aldosterone. AII causes Na and H2O reabsorption in the proximal tubule. AII also causes vasoconstriction....which is normal. Or is it? (no. it is not). Aldosterone still acts in collecting tubules to cause Na reabsorption.
74
Why isn't AII a solid vasoconstrictor in a pregnant woman?
RELAXIN (coming directly from corpus luteum), and local vasodilators far outweigh it. P4 is ALSO working to vasodilate. Don't forget that
75
How is AVP secretion affected?
P4 + E2 affects magnocellular neurons in the hypothalm to STIMULATE AVP secretion from Posterior pit. AVP binds to V1bR in anterior pit, leading to ACTH secretion, leading to the increase in glucocorticoids (think cortisol). AVP also binds to V1aR on vascular smooth muscle to ATTEMPT vasoconstriciton. This fails due to RELAXIN and progesterone. AVP still bonds to V2 in Kidneys to cause distal h2o reabsorption
76
How is GFR affected?
Decreased vascular resistance due to P4 leads to an increase in glomerular perfusion, and this increase GFR. The increased GFR would lead to lower plasma creatinine and BUN levels. However, it could ALSO lead to glucosuria due to oversaturation of SGLT channels...too much fluid being filtered.
77
Determinants of BP
BP = CO x TPR
78
How are the components of BP affected during pregnancy?
CO goes up (goes back tot the reduced peripheral resistance and placenta shunting) and TPR DECREASES due to relaxin, estrogen, PROGESTERONE, and nitric oxide. You may notice a decrease in diastolic pressure starting at end of first trimester due to the reduced TPR. These volues all normalize withing weeks 39-42 (birth)
79
What factors control a pregnant woman's blood gases?
1. RR
2. pH (and 2,3-BPG, and Temp)
3. Metabolic rate
4. CO
5. V/Q
6. Hb
80
What happens to the woman's rib cage during pregnancy? WHat lung pattern dows this resemble?
Softens the rib ligaments due to Relaxin (still from corpus luteum). As her uterus starts to increase in size, her lower chest diameter increases, and her diaphragm is pushed upwards into her lungs. THIS LEADS TO LAD!!! Note that this lowers her expiratory reserve volume (amount exhaled at top of quiet expiration) and functional residual capacity (ERV + RV), as lowers her chest wall compliance. Restrictive lung pattern.
81
How does progesterone affect the respiratory drive?
It stimulates medullary respiratory centers, increasing her minute ventilation (breaths per min)...30-50% increase, increasing her tidal volume.. Note that progesterone also lowers the threshold for CO2 sensitivity, making it even more sensitive to the presence of CO2 in the blood. In terms of the carotid bodies, the carotids increase sensitivity to hypoxia. and the increased metabolism of the woman increases CO2 production, which triggers the carotid chemoreceptors.
82
Describe the changes in arterial blood glasses in a pregnant woman , given that her ventilation is likely to have increased.
INcreased ventilation decreases PACO2 and increases PAO2. The increased PAO2 increases PaO2, where it can reach values above 100 in the first trim. There is a marked decrease in PaCO2, which furthers the gradient favoring offloading of FETAL CO2 into the mother. In terms of the mother, there is increase in maternal to fetal O2 transfer because the moterhe's PaO2 is now above 100. Gradients
83
What changes in the mother's acid-base status as a result of her changes in respiration?
The decrease in PaCO2 due to her increased RR leads to a respiratory alk. The kidneys compensate by excreting more HCO3.
84
Representative ABG in mother.
HCO3: 18-21
PaCO2: 26-32
pH: 7.44-7.45
(metabolic acid + respirt alk)...or just compensated chronic respiratory alk. THis is NOT an acute situation.
85
Describe the hb curve for the mom and the baby.
Fetal (left, red shift): Wants to dump of CO2 and uptake more O2
Maternal (right, blue shift): Wants to dump off more O2 and uptake more CO2.
Note that the mother has a physiologic anemia, decreasing her CaO2, but her O2 delivery is maintained due to increased CO.
86
Why is there a right, blue shift fostering a decreased affinity for O2 and an increased affinity for CO2?
1. Progesterone spiked up her body temp, which fosters O2 offloading and CO2 uptaking
2. Mom's metabolism is spiked up, so she's making a bunch of 2,3-BPG, which furthers the offloading of O2 and uptaking of CO2.
87
What happens to the mother during labor an delivery, with relations to cortisol?
CRH receptors are being expressed in pit, myometrial, and adrenals. Maternal adrneal produces a crap tone of cortisol because of CRH being released by the placenta. The increased cortisol production stimulates myometrium and starts contractions. The placenta's CRH also increases cortisol produciton in the kiddie. Cortisol us made and binds to the epit, adrenals,and lungs of the kiddie. The cortisol in the kiddie also produces surfactant and helps kiddie further mature. Note that kiddie starts making ACTH so causes release of its own cortisol instead o just that of placenta.
88
How does DHEAS affect the preganncy during labor?
Mother makes DHEAS from her adrenals, which is later converted to DHEA. THe fetal's adrenal straight up makes DHEA. THe DHEA increases the E3:E2 ratio even further, leading to the activation of more ER in the placenta. This leads to the expression of more myometrial contractile proteins, which causes myometrial to contract, just like cortisol did.
89
How does oxytocin and prostaglandins and an effective withdraw of P4 and loss of P4 RECEPTOR come into play during labor?
These all sync together to cause myometrium to contract more.
90
What is the corpus luteum doing during labor?
It is STILL producing Relaxin, but this time it's softening maternal pelvic ligaments. It also causes cervical ripening (flattening and distending of the cervix)
91
How does the baby avoid developing Cushings if the mom's cortisol levels is 5-10X higher than that of the kiddy's?
Kiddie takes the cortisol and converts it to cortisone with 11B-HSD2. Cortisone has a low affinity for the glucocorticoid receptors in the baby.
92
What is the danger to giving birth before 39 weeks?
Preterm births account for 70% of neonatal deaths. Anything lower is almost certainly a kiddie death sentence. Noe: normal term pregnancy is 39-42 weeks.
93
How does mother's body know that it's time to give birth?
Must realize that fetus grows throughout all 3 trimesters, and so does the uterus. However, a the end of the 3rd trimester, the uterus stops growing, despite the kiddie still growing. This Leads to increased uterine wall tension. The stretch on the uterus triggers mother to start contractions. Note that uterus also produces contraction-associated proteins which signal uterus to contraction.
94
What is significant about week 24?
This is the cutoff for preterm survival.
95
What do you do if woman is at risk for preterm delivery?
Prolong the delivery (becasue th efetus is still developing):
1. Give mother progestin: Stabilizes the myometrium
2. Give corticosteroids. this is to safeguard the fetus. If the delivery is coming regardless, you're are just gonna give mother this so that it can get to the baby and help it further develop.
2. Give a tocolytic agent (competitive Ca inhibitor) to stop contractions because uterus is still muscle.
96
Woman looks straight up healthy, and yet she is infertile. She has given birth before. Suggest some possible reasons for infertility
1. Implantation issue
2. Not enough follicles
3. Fertilization issue. Sperm just not compatible
4. Immunity issue
5. Chromosomal quality...something wrong with oocyte or sperm
6. Uterine pH could be incompatible
97
T or F: Biphasic BBT is normal
T
98
How to diagnose ovulatory dysfunction
Presents with irregular menses, and she may be really fat or really skinny. Diagnose with BBT, and check LH surge
99
How to diagnose uterine disorder
Presents with heavy menses (heavy bleeding during period) and pain. Diagnose with HSG test
100
How to diagnose tubal disorder
PResents with histor of chlamydial or gonococcal infection. Diagnose with HSG.
101
How to diagnose peritoneal factor comlication
(idea that endometriosis has problem). Patient presents with dyspareunia, dysmenorrhea, dyschezia (painful intercourse, painful menstruation, painful defecation). Diagnose with lapaoscopy.
102
What causes lactation during gestation? What prevents milk let-down (secretion) during gestation?
Estrogen causes production of prolactin. Prolactin is the hormone responsible for milk production (lactation). Estrogen and progesterone had both, up until that point, been responsible for preventing milk-let down (secretion)
103
What is the inhibitor for prolactin secretion?
Dopamine
104
What do estrogens and progesterones due for breast development during gestation?
Estrogens stimulate development of breast ductal epithelium and progesterone stimulates breast alveoli (nipple region).
105
What happens post-partum (after birth) of baby, with regards to lactation?
E and P4 plummet, and there is direct wiring associated with the baby suckling on nipples.
1. This ends the preoptic nucleus of hypothalamus, leading to the inhibition of GnRH. This stops gonadotropin production. Which is why woman nursing her baby will not cycle. Cycling is inhibited.
2. Causes further production of prolactin, which both further stimulates lactation and further inhibits gonadotropin production. Prolactin DIRECTLY inhibits gonadotropin production. Prolactin excess = infertility/amennorria
3. Causes further production of oxytocin, which causes milk secretion (milk-let down)
106
T or F: Anything that appears to be menopause before age 40 is pathologic
T. Likely ovarian failure. You must know that 40 yr old is the cut-off.
107
Describe oogenesis setup prior up to puberty
Upon sexual differentiation, the female has 6mil eggs. At birth, the baby has about 500k. For the next 10 to 12 years, folliculogenensis is occurring, but eggs still go through atresia. At puberty, there is only 30k eggs left. The eggs being referred to throughout all of this is primordial up until the 10-12 years old. Note that in puberty the GnRH puls gen is finally activated.
108
Describe oogenesis lifetime from beyond puberty
With the remaining 30k eggs, ovulation occurs for 4-5 decades, going through recruitment, selection, ovulation, and atresia in each cycle. By the time woman reaches menopausal transition, within the remaining 2 years of reproductive viability, the follicular reserve is exhausted and there are less than 1000 primordial eggs in each ovary. Note that FSH increases, Estrogen plummets, AMH decreases, and there is ovarian failure.
109
How does anti mullerian hormone (AMH) act as a marker of fertility?
It represents the number of healthy growing follicles in a woman. AMH is secreted by the granulosa cells in preantral follicle. AMH legitimately governs how many primordial follicles are recruited during the recruitment phase.
110
Describe the relationship between the amount of recruitment that occurs in female life and the amount of AMH present. When is peak fertility?
As AMH increases throughout the woman's life, the amount of folliceles recruited in a cycle also increases. Peak fertility occurs at the time where AMH reaches max production, which directly indiccates a maximum amount of healthy growing follicles in the woman's life. This correlates with a high (not the highest tho) amount of egg recruitment. This occurs around her mid 20s.
111
What happens is AMH is low relative to reference standards?
She does not have enough healthy growing follicles, which explains any potential fertility she may be having.
112
Describe menopausal transition
Around age mid 40s to early 50s, after about 4 decades of menstration, woman will see elevated FSH from normal and a falling E2. FSS:E2 ratio WILL increase. Her cycles will become more variable, some months will be skipped, appearing like amenorrhea. Some cycles will be longer than others. Note that this would NOT happen prior to age 40, otherwise pathologic. There will be a point around age 51 where FSH:E2 ratio is even higher than prior, and she will have had her last period. She would not know it. Menopause is deemed 1 year after her last period.
113
List criteria for primary ovarian insufficiency (premature ovarian failure)
1. Below age 40
| 2. High FSH:E2 ratio
114
Describe the menopausal transaiton in relation to amh, E2 and FSH
Recruitment of follicles leads to their growth. The growing follicles secrete AMH, as well as E2 and Inhibin B. E2 and Inhibin B BOTH inhibit FSH production. Both Inhibin B and E2 are coming from granulosa cells. Remember that T is being bade from the Thecca cells, and then being converted by the granulosa cells with CYP19. Remember that AMH regulates the amount of follicle allowed to enter the growth pool.
115
How do FSH and AMH and E2 operate when the follicular reserve deminishes?
Diminishing follicular resercve deminishes the whole AMH and E2 and Inhibin B production. So FSH is not as checked as it once was, hence it's steady incline over E2. FSH is less held back, and the FSH is now being even more bathed by FSH, so there is an accelerated rate of folliculogenesis and accelerated loss of follicular reserve. Also note that the weakened production of AMH means that there is less, if any governing of the amount of follicles being released, so they too come out unchecked.
116
Describe the decline in fertility in woman paste 35
Graph shows stead decline in AMH from 35-37 onward. This means less healthy follicles are being recruited, meaning less of a pool secreting the necessary vast bath of hormones, including E2 and Inhibin B, meaning less FSH inhibition. This all also leads to the more irregular periods. Essentially, she can still get pregnant at 40, but she just does not have the proper endocrine support to allow ovulation of a healthy egg. Note that AMH is measured in these women to see just what her chances are to get pregnant, and monitor her protocol to account for the amount of eggs she has left, based on this AMH amount.
117
What is the reason for significant decline in female fertility beginning at 35?
Loss of ovarian function. Loss of ovarian follicles + loss of E2 production.
118
What is the problem leading to decreased fertility? Is it the eggs or is it the uterus? Why?
It's the eggs because eggs taken from 29 yr olds and implanted in 40 year olds have way higher success rates in childbirth than eggs used from the 40 year old and implanted back into said 40 year old. If it was a uterine problem, there would still be a steady decline in successful births, despite the implantation of the younger eggs.
119
How does cryopreservation work? Is it effective?
Woman comes at prime age to doc, has eggs taken and frozen. Plans to implant them at an older age. The stats show a 10% live birth success if the eggs are retrieved before age 36. Retrieved after 36, and that success rate becomes 3% or less. So yes, it works.
120
Describe relationshio between woman in advanced fertility age and incidences of embryo aneuploity and maternal mortality.
An women age, there is an increase in both embryo aneuploidy and maternal mortality. They both steadily go up on the same plat. Don't try to conceive at or above 35! It could literally kill you due to complications. The pregnancies could even self abort. Note that maternal deaths increase too, by a lot.
121
How to treat menopausal patients
Note: These women are coming in with hot flushes.
With a uterus: If woman has a uterus and she is a candidate for hormonal therapy, give her BOTH E2 and P4. Reason: E2 causes endometrial lining proliferation. P4 stops this uncontrolled growth. if P4 is not give, will lead to endometrial cancer. This is essentially an E2 + P4 contraceptive. She still has a period to get rid of endometrium.
Without a uterus: If she is a candidate, you don't need to give her P4. Just the E2.
You would NOT be a candidate if you have a history of cancers or strokes, or if you have elevated VTE (ability to make plots). note that hormonal therapy would still have cardiovascular risks
If woman is a candidate, you start the therapy in the younger menopause person for about 3-5 years. The symptoms will go away eventually.
122
T or F: Taking birth control prolongs fertility lifespan
False. She is still recruiting follicular reserves, and she is still having follicles go through atresia. Note, starting from first period, about 500 eggs ever go on to be recruited to ovulate. The rest die.
123
What is PCOS
Polycystic ovarian syndrom. About as common as insulin resistance. Patients normally present with irregular menstrual cycles and anovulation. However, they more importnantly present with hyperandrogenemia dur to their ovaries. Androgen refer to T specifically.
124
What disease MUST be ruled out before making this diagnosis?
Congenital adrenal hyperplasia (CAH) (adrneal cortex disease, resulting in a loss of one or more biosynth enzymes resulting in loss in ability to make cortisol or cortisol, and so they make more androgens instead or glucocorticoids and mineralcorticoids. So they make a TON of DHEAS and androsteindione, which are both used to make T.
3. Hyperprolactinemia: too much prolactin in blood, so they are infertile
4. androgen -producing adenomas: Something in the ovaries, specifically the thecca cells, are pumpin out androgens
5. Cushing's syndrome
125
T or F: Woman does not need to have cystic ovaries to be diagnosed with PCOS
T or F: Polycystic ovaries do not ovulate
1. True. This has since been removed from the criteria.
| 2. True, they do not ovulate
126
Describe the insulin-resistance model of PCOS
You need to realize that LH massively increases the amount if T made by thecca cells, compared to when LH is not there. This is because, LH secreted targets the Thecca cells, and uses CYP 17 to convert and crank out T. If this process is accelerated, the woman will have hyperandrogenemia. This becomes hyperandrogenISM if it gets high enough. In the case of Visceral fat, adipose presence leads to insulin resistance (adipose releases cytokines that sabotage insulin). The resistance leads to hyperglycemia and thus hyperinsulinemia. And the hyperinsulinemia further increase hyperandrogenemia. It just so happens that Lh + insulin = synergy effect i which you have an exponential increase in T production.
127
Why is it that a woman producing too much T becomes anovulatory?
Negative feedback on gonandotropin production caused by the increase in T production. No gonadotropins = no ovulation. The lack of ovulation means there is no corpus luteum, by definition. This means no P4 spike. This means not negative feedback on LH (which already, by definition, causes thecca cells to make T). This means an increased LH:FSH ratio. Which means an increase in LH. THe insulin casued by the insulin resistance only unites with LH to spike androsteindione and T production...T is the culprit tho. These androgens specifically cause the formation of anovulatory cyctic follicles. However, the androgens are also still aromatized into E1 and E2 by granulosa cells. Should also note that visceral fat also expresses CYP19...not just the granulosa cells. All this estrogen also leads to increased negative feedback on FSH, which also leads to formation of anovulatory cystic follicles. Bone is unafected, despite the increase in E. They are actually happy. This woman presents very young (teenage/20s), heavy in that their fat distribution is skewed to be viscerally distributed.
128
Difference between hyperandrogenEMIA and hyperandrogenISM
```
EMIA = measurement
ISM = the presentation/manifestation of the elevated androgens
```
129
How do you know person has hyperandrogenemia?
1. Hirsutism (hair on face/chest, back)
2. Thinning
3. Voice deepening
130
What are the 4 syndromes of metabolic obesity?
1. DM2 (truncal obesity, HTN, and dyslipidemia)
2. PCOS (anovulation, truncal obesity, insulin reisstance, irregular cycles)
3. MetabolicSyndrome (insulin resistance, HTN, and dyslipidemia, increased waist to hip ratio)
4. Truncal obesity and insulin resistance
They all have truncal obesity and insuline reistance.
131
Why do we worry about PCOS patients?
Could develop cardiovascular disease because of the dislipidemia.
Could even more importantly develop DM2 (HTN, dyslipidemia). Could also develop endometrial cancer since all the T and androstedione is being converted to E2, which proliferated the endometrium without the presence of P4. Unopposed E = bad. Endometrial risk is the largest risk here. Period.
132
T or F: hyperandrogenemia exerts negative feedback on FSH secretion
T
133
Describe Adrenal cortical model of PCOS
Woman's adrenal cortex churns out DHEAS and is converted to androstenedione and T with 17B-HSD enzyme in thecca cells. In these women tho, DHEAS is very elevated, so more T is produced.
134
What is significant about the frequency of Lh production in PCOS patients?
It is incredibly spiked. We're talking double vs single digits. These patients are lacking P4.
135
How does one treat PCOS?
First tactic: weight loss (bmi of 28 and up). You would do the same with DM2 patients.
136
How do you protect patients uterus with PCOS from unopposed E2?
Give birth control pills which cause a negative feedback, disabling GnRH and thus gonadotropin secretions. Goal is to decrease LH. Decreasing LH prevents androgen synth in thecca cells. This deals with the hyperandrogenemia issue too. You would NOT just give her progesterone because she is a young woman. She needs E for bone protection and for the cardiovascular benefits. Note that is you lose E, regardless of age, you will show menopausal symptoms. You would not use metformin. Only use this for women WITHOUT PCOS and has hyperglycemia. You COULD conceivably use aromatase inhibitor to deal with E2 production, but it does not finish off the problem entirely. Could also use spiranolactone since it acts as an androgen receptor antagonist, but it is not the first choice..
137
Describe the prescence of preovulatory follicles and primordial follicle in a transitioning menopausal woman, relative to non menopausal.
Primordial follicles: Decreased
Preovulatory follicle: may or may not be present.
Amount of growing follicles: Decreased
