Physio Flashcards
1
Q
- The menstrual cycle is composed of both the ovarian and uterine cycle.
- The ovarian cycle is divided by ovulation into the follicular phase and the luteal phase.
What is the uterine cycle divided into?
A
Proliferative phase and Secretory phase
note: ovulation causes the transition from one phase to the next in both the uterus and ovary
2
Q
The arcuate nucleus stimulates GnRH release. Which form of GnRH is the physiological relevant form?
What is the major control mechanism for release of GnRH?
A
GnRH-1 Ultradian cycle (28 days)
(also: Estradiol, leptin, NPY, Norepi, circadian clock)
3
Q
What effect do these have on GnRH? B-endorphin GABA Dopamine Estradiol
A
Inhibitory
4
Q
TQ GnRH is released in a pulsatile manner. In what phases do the 2 different pulse cycles occur? What are the pulse rates? What are the hormones that are released?
A
Follicular/proliferative phase:
- Early in cycle to ovulation
- Every 90-100 min, promoting FSH
Luteal/secretory phase:
- After ovulation
- Every 3-5 hours, promoting LH release
5
Q
The GnRH receptor (2) is expressed on gonadotropes in the ant. pituitary.
GnRH-R1: Gq11R»>incr Ca intracellularly
What is GnRH-R2 MOA?
A
Transcription and translation of genes coding for FSH and LH
6
Q
- FSH and LH are considered glycoproteins of the ant. pituitary. Therefore, they both have an alpha-subunit. However, each has their own specific B-subunit. Each has a distinct Gs coupled receptor–>cAMP–>PKA
- What accounts for their differences in HL? What are each of their half lives?
A
FSH: 170 min (greater due to incr glycosylation)
LH: 60 min
They glycosylated which leads to differences in their HL.
7
Q
Drive the developing follicles to produce steroid hormones estrogen and progesterone, as well as androgens.
A
FSH and LH
8
Q
Predominates in the follicular/proliferative phase and contributes to ovulation.
A
Estrogen
9
Q
What are the steps of estrogen production? (FSH)
A
1) Thecal cells convert cholesterol to androstenedione.
2) Androstenedione is transported to the granulosa cells
3) Granulosa cells have aromatase, which converts Androstenedione–>Estradiol
10
Q
TQ
- There are 2 estrogen receptors (alpha and beta) produced by alternative splicing.
- ER are members of the nuclear receptor family (pass through membrane–>nucleus).
- 2 activation factors, a DNA binding domain, and a ligand binding domain
Which activation factor domain is associated with the ligand binding domain?
A
AF2
AF1 is NOT assoc. with binding…estrogen–>AF2–>effects!
11
Q
The ligand binding domain of estrogen R is very large. What is the result of this?
A
A number of loosely related structures can fit into the receptor (agonists/antagonists).
Ex: Tamoxifen: long side chain prevents change in conformation of receptor, preventing activation and binding to DNA
12
Q
How does estrogen act through AF2?
A
Steroid into nucleus>> Binds to ER>> Dimerizes with another E/ER complex>> Activation factors + DNA binding region interacts with DNA>> Alters transcription
13
Q
TQ
How does estrogen act through AF1?
A
AF1 is on the cell membrane so estrogen acts as a second messenger system (Gs)
14
Q
Why are exogenous agonists and antagonists often classified as partial/mixed? AKA they may act as an agonist in some functions but an antagonist in others.
A
Flexibility of the estrogen receptor due to its large ligand binding domain and the 2 different types of receptors.
15
Q
Predominates in the luteal/secretory phase and prepares the body for pregnancy
A
Progesterone
16
Q
What are the steps of progesterone production? (LH)
A
1) Thecal cells convert cholesterol to androstenedione and pregnenolone
2) Androstenedione and pregnenolone are transported to the granulosa cells
3) Granulosa cells respond to both LH/FSH convert androstenedione to progesterone (pulses of 3-5 hrs)
17
Q
- There are 2 progesterone receptors (A and B form)
- It has 2 activation factor sites (vs. estrogen=2)
- Which activation factor is associated with the ligand binding domain?
A
AF2
18
Q
Which of the following exerts the greatest stimulatory effect on the release of GnRH? A) B-endorphin B) Dopamine C) GABA D) Leptin E) Ultradian rhythm
A
E) Ultradian rhythm
A-C) Inhibitory
D) Permissive
19
Q
GnRH is released in pulses every 90-120 min. What hormones are preferentially being secreted? A) Androstenedione B) Estradiol C) Luteinizing hormone D) Progesterone
A
B) Estradiol
FSH–>Estradiol!
20
Q
Which of the following hormones binds to a ligand binding domain that is very large and associated with activation factor 2 and a DNA binding domain? A) Estradiol B) Follicle Stimulating Hormone C) GnRH D) Luteinizing hormone E) Leptin
A
A) Estradiol
21
Q
What are the two gonadotrope independent stages of ovarian follicle development?
A
Primordial and Pre-antral
22
Q
Transitioning a follicle from the dormant to the growth phase requires interaction b/t the ovum and granulosa cells.
What is secreted from the ovum that leads to pre-antral–>antral stage?
A
Step 1:
-Ovum secretes bone morphogenic protein (BMP-15) and growth differentiation factor (GDF) that cause granulosa cells to become cuboidal
Step 2:
-The granulosa cells secrete c-kit (kit ligand…receptor on ovum), which removes the ovum from inhibition that prevents its growth.
23
Q
Which stage marks the beginning of gonadotrope dependent follicle maturation?
A
Antral stage (growth)
24
Q
About 85 days prior to ovulation, hundreds of follicles enter the selection growth phase. What will these follicles secrete?
A
AMH (anti-Mullerian Hormone)
25
During the follicluar/proliferative phase, GnRH release is stimulated by time and inhibited by estradiol (neg feedback).
However, the GnRH neurons do NOT express ER.
How does estrogen inhibit GnRH? What are the NT involved?
Incr estrogen>>
Decr Kisspeptin/NKB/dynorphin>>
Decr GnRH release>>
Decr FSH/LH
Polysynaptic pathway: The ER are found on a diff. neuronal pop. in the arcuate nucleus w/ their own NTs. The GnRH neurons in the hypothalamus express receptors for these NT. The NT are:
- **Kisspeptin
- Neurokinin B
- Dynorphin
26
TQ
T/F
The release of Kiss1/NKB/dynorphin onto the GnRH releasing neurons of the hypothalamus INCREASES GnRH release.
True!
27
TQ
| How does estrogen decrease the release of Kiss1/NKB/dynorphin?
Estrogen response element (nuclear R)
28
In the follicular phase of the ovary, the high estrogen concentration promotes development of the follicles from the previous cycle that have been chosen in the selection growth phase (AMH).
The ovum that will be ovulated will additionally secrete what factors? why?
- Estrogen-->Incr FSH receptors-->Incr FSH sensitivity....allows the ovum to continue to develop even when the FSH levels fall b/t the two cycles
- Inhibin A and B are also released
29
During the proliferative phase of the uterus, estradiol from the ovary promotes endometrial growth (1-2 mm to 6-10 mm) by increasing growth factors. What does this lead to?
- Elongated glands (dont secrete)
| - Spinal artery extension through increasing thickness
30
What changes does the myometrium undergo during the proliferative phase?
- Incr expression of oxytocin receptors
- Incr expression of contractile proteins
- Incr excitability of the smooth muscle
(ready to respond to ovulation)
31
Negative feedback between estrogen and FSH occurs pre-ovulation and during the luteal/secretory phase. Positive feedback between estrogen and LH is required for ovulation. How does this occur?
- A second set of KISS1/NKB neurons are located near the AVPV anteroventral periventricular nucleus (3rd ventricle).
- These neurons express ER but are NOT mediated through the estrogen response element
- Instead, cell membrane R-->phosphorylation of proteins-->incr in GnRH and LH.
32
```
Activation of what receptor type leads to apoptosis of thecal cells and eventual ovulation?
A) ER-alpha
B) ER-Beta
C) PR-A
D) PR-B
E) PR-C
```
C) PR-A
Ovulation requires the expression of progesterone receptors (PR-A)>>
Cytokines and proteases>>
Apoptosis of thecal cells>>
Follicle rupture and release of ovum
33
```
Secretion of what chemical identifies an ovum as having entered the selection growth phase?
A) Bone-Morphogenic protein (BMP)
B) Anti-Mullerian Hormone (AMH)
C) C-kit
D) Growth Differentiation Factor (GDF)
E) Inhibin A
```
B) Anti-Mullerian Hormone (AMH)
A, C, D) Before growth phase (pre-antral-->antral...gonadotropin dep)
E) "Ovulated" ovum
34
```
A neuron that releases Kisspeptin, NKB, and dynorphin is found to be inhibited when estrogen binds to its receptors. Where is this neuron located?
A) AVPV
B) Arcuate Nucleus
C) Paraventricular nucleus
D) Supraoptic nucleus
```
B) Arcuate Nucleus
35
- After ovulation, in the luteal and secretory phase, LH stimulates the granulosa and thecal cells to differentiate into granulosa and thecal lutein cells.
- The decr in FSH and incr in LH receptor activity-->expression of different steroid synthetic enzymes, including progesterone.
What are some of the actions of progesterone?
Promotes the secretory function of the endometrium:
* -Glands accumulate glycogen and secrete glycoproteins, proteins, and transudate of plasma-->lumen
- Spiral arteries coil/corkscrew
- Incr capillary permeability (transudate)
- Pre-decidualization occurs-->incr PG (getting ready for implantation)
Decreases excitability/contractility of the myometrium (decr estogen and oxytocin R) w/ continued SM growth (hyperpolarized...no contraction)
36
About 9 days post-ovulation, the corpus luteum will undergo apoptosis and progesterone levels fall-->shedding of endometrium.
However, if a pregnancy occurs, what prevents the apoptosis?
Human chorionic gonadotropin (hCG)
37
When apoptosis/regression og the corpus luteum occurs, the endometrium secretes PGF (2alpha) and PGE2.
What do the PG's do?
(note: The decr in progesterone also triggers secretion of matrix proteases adding to the regression)
Cause spinal arteries to constrict blood flow>>
Ischemic endometrium>>
Shedding
38
What is blood loss in menses limited by?
- Blood clots
| - Estrogen-induced healing of basalis layer by epithelial cell replacement
39
GnRH pulses are measured in a women and found to be occurring every 3-5 hours. What else is happening at this time?
A) Uterine glands are elongating
B) Incr oxytocin R expression in myometrium
C) Incr LH secretion
D) Neurons in AVPV secreting Kisspeptin
E) Apoptosis of follicular thecal cells
C) Incr LH secretion
A) follicular/prlife
B) estrogen
D LH surge ovulation
E) Ovulation
40
Reproductive hormones remain low until age 6. What happens?
GnRH pulses at NIGHT
- Clock, BMAL1, period gene dependent
- DONT lead to significant FSH and LH release (no daytime pulses)
41
TQ
| What causes the GnRH pulses at night at about age 6?
- Catecholamines and EAA (via NMDA) receptors acting on GnRH neurons
- PGE2 (glial cells, triggered by TGFa)
42
What is important step in the production of puberty and why?
hint: puberty=GnRH-->ultradian pattern
AVPV KISS1/NKB neuron development-->
Positive feedback-->
LH surge
43
T/F:
If given kisspeptin, onset of puberty is accelerated.
If antagonize its receptor (KISS1R), puberty delayed.
True
44
Leptin's role in puberty is permissive:
Which cells involved in GnRH secretion have the leptin receptor?
Note: giving leptin does NOT advance puberty and puberty occurs slowly in leptin deficient individuals.
- KISS1/NKB cells of both the arcuate and AVPV DO....leptin helps them come to threshold
- GnRH releasing cells of arcuate nucleus do NOT express the leptin receptor
45
- Cessation of menstraul cycles in women at avg age 52 yo
- High gonadotropic hormones, low estrogens, and progesterones
- Exhuastion of the supply of follicles for development
- Failure of follicles to secrete estradiol-->no negative feedback-->FSH LH incr
- Degeneration of KISS1/NKB neurons in AVPV
Menopause
46
5-year old girl shows GnRH pulses at night. Which NT are producing these pulses?
A) Kisspeptin and dynorphin from AVPVn neurons
B) Kisspeptin from arcuate nucleus
C) Catecholamines and EAA from arcuate neurons
D) PGE2 from AVPV neurons
C) Catecholamines and EAA from arcuate neurons
D) PGE2 from glial cells!
47
During the uterine cycle, glands secrete glycoprotein and protein rich exudate to provide nourishment before implantation.
What is pre-decidualization?
Changes in the endometrium that will render it "hostile" to implantation
Therefore, Blastocyt has limited window to implant (8-10 days after ovulation)
48
TQ
- In direct contact with maternal circulation
- Contains machinery for formation of pregnancy hormones such as hCG, hPL, and CRH
Syncytiotrophoblast
49
What hormone?
- First measurable product of placenta
- Has identical alpha subunit as LH, FSH, and TSH
- **β subunit is more specific (67% homology to LH)...acts like LH to maintain corpus luteum
Human Chorionic Gonadotropin (hCG)
50
TQ
- What stimulates the release of hCG?
- What are some functions of hCG?
- Stimulus: placental GnRH
- Maintains corpus luteum>>>
- Promotes progesterone secretion by corpus luteum
- Fetal testicular testosterone secr.
- Maternal thyroid stimulation
- Peaks @ 10 wks then decr.
51
What hormone?
- Human somatomammotropin
- Part of growth hormone family
- Detectable levels @ 4-5 weeks gestation
- Secretion approaches 1g/day!!
- Control of secretion: constitutive?
Human Placental Lactogen (hPL)
52
What are some functions of hPL?
Hint: member of GH family
- Contributes to altered glucose metabolism in woman (diabetogenic)
- Mobilizes free fatty acids
- Directly stimulates release of insulin
- Contributes to insulin resistance associated with pregnancy
- Maybe angiogenic to fetal vasculature
53
What hormone? 
- Directly incr DHEA-S from adrenals to make estrogen (timing of parturition)
- Directly increases chorionic ACTH (not maternal ACTH)
Corticotrophin Releasing Homone (CRH)
- Identical to hypothalamic form
- Detectable levels in serum occur late in gestation and peak at labor/delivery
54
TQ
How does fetal adrenal cortisol influence placental CRH?
(positive/negative feedback)
Positive feedback mechanism!!
55
TQ
CRH-->incr fetal ACTH-->cortisol production
Whats the importance of cortisol production by CRH?
Fetal lung maturation (make surfactant)
56
What hormone?
- Takes over from the corpus luteum at about week 8.
- Secretion will continue throughout pregnancy
- Made from maternal LDL cholesterol
- Maintains uterine SM quiescence during pregnancy
Progesterone
57
```
TQ
What hormone?
-Increases throughout pregnancy
-Made from DHEA-S of fetal & maternal adrenal glands (NOT progesterone)
-Indicator of fetal well-being
```
Estrogen
58
```
TQ:
Production of which of the following hormones requires that the fetal adrenal gland be functional?
A) hCG
B) hPL
C) Relaxin
D) Progesterone
E) Estrogen
```
E) Estrogen
Fetal well-being!!
Fetal demise rapidly reduces estrogen synthesis (not surprising)
59
Hormone?
- Peptide hormone structurally related to insulin
- Produced by decidual cells of the ovary
- Peaks @ 14 wks gestation and @ labor/delivery
- Functions traditionally to relax pelvic ligaments
- Role in maternal cardiovascular changes that occur with pregnancy
Relaxin
60
```
Secretion of which placental hormone is controlled by placental GnRH?
A) hCG
B) hPL
C) CRH
D) Progesterone
E) Estrogen
```
A) hCG
B) feeds baby, continuous
C) contractility
61
```
What is the source of relaxin during pregnancy?
A) Anterior pituitary
B) Hypothalamus
C) Placenta
D) Ovary
```
D) Ovary
62
TQ
Name the hormone:
-From placenta
-Released in response to GnRH
-Initial appearance 1 day after implantation
-Peaks 60-90 days
-Functions to maintain corpus luteum-->progesterone
hCG
63
```
TQ
Name the hormone:
-From placenta
-Continuous release
-Initial appearance 20-40 days
-Peaks at term
-Mobilizes maternal energy supplies (diabetogenic)
-Part of a large family of growth hormone related proteins
```
hPL
64
```
TQ
Name the hormone:
-From placenta
-Positive feedback from cortisol
-Initial appearance in wk 7 (incr in last 10 wks)
-Peaks at term
-Incr ACTH/cortisol/DHEA-S
-Incr Fetal lung maturation (surfactant)
-Parturition
```
CRH
65
```
TQ
Name the hormone:
-From ovary/placenta
-Released in response to hCG
-Peaks at term
-Uterine quiescence
-Requires LDL-cholesterol from maternal secretion
```
Progesterone
66
TQ
Name the hormone:
-From ovary/placenta
-Released in response to hCG
-Peaks at term
-Involved in uterine growth and incr in uterine blood flow
-Requires precursors from fetal and maternal adrenals
Estradiol
67
```
TQ:
Name the hormone:
-From the ovary
-Peaks at 14 wks & delivery
-Causes pelvic "relaxation"
-Maternal CV changes
-Structural similarity to insulin (aa homology
```
Relaxin
68
TQ
Near term, the utero-placental blood flow may be 450-650 mL/min (10% cardiac output)
:( kidney and brain
What are the 2 components to this increase?
1) Incr maternal-placental blood flow:
Estrogen--> vasodilation & decr response to AT II
2) Incr fetal-placental blood flow:
Incr progesterone-->Incr placental blood vessels
69
TQ
-The placenta is a HUGE vascular bed added to the circulatory system of the pregnant woman.
-The vasodilation & addition of the vascular bed causes what change in the mother?
Decr in maternal TPR of about 20% (more so diastolic)
| Decr BP of mom
70
TQ
- Maternal cardiac output is increased by wk 6 & peaks in the 3rd trimester (> 6 L/min=50% increase)
- Early increase in CO is mediated by what hormone?
Estrogen
Increase venous return, preload, and stroke volume
71
-Enlarging uterus can physically block circulation to lower extremities by compressing vena cava and aorta
What becomes very important?
Physical positioning
```
Supine (higher BP)
Lateral recumbent (lower BP)
```
72
Throughout pregnancy, we see a 50% increase in blood volume.
Why does the plasma volume expand more than the red cell volume? (decr in hematocrit)
The RAA axis (plasma volume) has a greater effect than the incr in EPO (red cell volume)
73
TQ
| Is plasma osmolarity increased or decreased in pregnancy? What does this lead to?
Decreased (incr in volume)
Resets the osmoreceptors in the brain so that they recognize the dilute blood as normal
74
What causes the hypercoaguable state in pregnancy?
hint: BC-->hypercoag.
1) Estrogen-->
- Incr fibrinogen, factors V, VII, VIII, and X
- Incr D-dimer
- Resistance to activated protein C
2) Venous stasis
75
Why do many pregnant women experience nasal congestion ?
Incr progesterone! >>
Upper airway hyperemia, glandular activity, & edema
- Increased progesterone can lead to incr respiratory drive and incr oxygen consumption
- Increased minute ventilation by inc VT (deeper breathing)
76
Why do pulmonary function tests show minor changes in FRC, RV, and ERV in pregnancy?
Elevation of the diaphragm
77
In pregnancy, there is an increase in minute ventilation. What does acid/base status does this lead to in the mother?
```
-Compensated
respiratory alkalosis
-pH=7.4–7.45
-PaCO2 drops to 28–32 mmHg
-HCO3 ~ 22 mEq/L
-PaO2 is elevated (100 -105 mm Hg)
-In order to maintain fetal PaO2 at 70 in most saturated blood
```
78
Incr kidney size during the pregnancy:
- Dilation of the vasculature (increased blood volume)
- Dilation in the collecting ducts
What hormones cause this change?
Progesterone (& relaxin)
79
What changes will we see in renal plasma flow, GFR, and filtration fraction in pregnancy?
Why is this impt?
- Incr renal plasma flow
- Decr GFR
- No change in FF
Incr clearance of freely filtered and excreted drugs
(may be countered by decr blood concentration & incr in blood volume)
80
What has a higher excretion rate in pregnancy?
hint: change in podocyte polyanionic proteins
-Protein/albumin (300mg/day) -Glucose
81
-The fetus will require 50-100g of glucose/day by the 3rd trimester
So what alterations in glucose homeostasis might we see in the mother? What hormone mediates this change?
-Early:
Decreased blood glucose>>
Increased ketogenesis
-Later: Insulin resistance
- Lower fasting glucose
- Incr blood glucose w/ ingestion
- Incr insulin response w/ ingestion
- Mediated by hPL
82
-ACTH, cortisol, and thyroid hormone levels all increase during pregnancy.
What happens to PTH?
Decreases
| Incr 1,25-vit D (placental)
83
```
Parturition:
Incr _______ (incr DHEAS)>>
-Incr gap jx in myometrium (uterine excitability)
-Incr oxytocin R
-Incr oxytocin prod by uterus
-Incr PGE2, PGI2 PGF2alpha prod by uterus
>>>
-Incr contraction of uterus
-Incr dilation of cervix
>>
-Incr release of oxytocin from pituitary>>
-Incr contraction etc
```
estrogen
84
```
Parturition:
Phase 1=Quiescence
-Progesterone
-Prostacyclin
-Relaxin
```
Phase 2=Activation
- Estrogen
- Progesterone
- _______ ______
Phase 3=Stimulation
- Prostaglandins
- Oxytocin
- Relaxin
- CRH?
BIRTH
Uterine stretch
85
Describe mammary gland development during puberty and menarche
Note: These changes regress if don't become pregnant
Puberty:
Estrogen-->ductal growth/branching
Menarche:
Progesterone & estrogen-->
ductal growth and formation of rudimentary alveoli
86
How do estrogen and progesterone affect mammary gland development in pregnancy?
note:
Estrogen: direct effect, mediated via prolactin
Progesterone: direct effect
- Further ductal and alveolar growth
| - The alveolar epithelial cells will express genes coding for milk proteins and enzymes to produce them
87
How does lactation begin after birth?
note:
-Colostrum is secreted from the breast - high in antimicrobial
and anti-inflammatory proteins.
-Normal milk production will take days to occur b/c the breast must ‘recover’ progesterone’s inhibitory influence
1) Prolactin (no longer stimulated by estrogen)>>
- Formation of milk
- Secretion into ducts
- Inhib GnRH secretion (lactational amennorhea)
2) Suckling by the infant>>
- Release of oxytocin
- Binding of oxytocin to its receptor causes contraction of the myoepithelial cells
- Leads to milk letdown (expulsion of milk from breast)
88
Which of the following conditions is required to prevent the decrease in progesterone during the luteal phase?
A) Production of hCG by the fetus
B) Expression of LH and FSH receptors on follicular lutea cells
C) Expression of PRA on the follicular granulosa cells
D) Expression of KISSR1 on hypothalamic neurons in the AVPV
A) hCG
89
Which of the following actions is produced by secretion of the placental hormone hPL? (detectable at 10 wks and peaks at 40 wks gestation)
A) Insulin resistance
B) Promotes progesterone secretion
C) Increased secretion of pulmonary surfactant
D) Increased uterine smooth muscle excitation
A) Insulin resistance
| CRH starts later
90
A 30 yo presents in 32nd wk of pregnancy w/ CC: progressive swelling in rt arm. Cyanosis present in extremity and radial pulse +2/4. Pt is up to date on prenatal care and pregnancy has been normal. Incr (WNL for preg) of favors V, VII, VIII, X, d-dimer, and act. protein C resistance. What is the direct cause of the changes in the pt's coagulability?
A) Estrogen
B) Progesterone
C) Relaxin
D) Prostaglandin E2
A) Estrogen
High bleeding risk bc of the placenta so body incr clotting factors!
91
```
A kindred is identified as suffering from a loss-of-function mutation in a protein involved in normal reproductive maturation. In the protein's absence, the onset of puberty is delayed or absent in the female members of the family. If the protein is replaced via injection, puberty occurs normally and the protein does not advance the onset of puberty if given prior to puberty. What protein is affected by this mutation?
A) Kisspeptin
B) Dynorphin
C) Leptin
D) NKB
E) GnRH
```
C) Leptin
Didn't advance the onset of puberty (Kisspeptin does)
92
During a routine ultrasound exam, regular fetal respiratory motions were detected. What other behaviors/events were occurring simultaneously?
A) Rapid eye movements
B) The diving reflex
C) Suckling movements of the mouth
D) Voluntary motion, including trunk rotations
A) Rapid eye movements
Respiratory motions=REM sleep
93
32 yo woman presents w/ hx of irregular menstrual cycles. Menarche occurred at age 18 and her cycles have never been regular. Physical exam is significant for a BMI of 31, acne, and hirsutism. She and her husband have been trying to conceive a baby for the past 18 mo, but cannot. An excess of which hormones is likely to be present in this patient?
```
A) Progesterone
B) Testosterone
C) LH
D) hCG
E) Cortisol
```
Determined that GnRH pulses are every 60 min, regardless of where in the menstrual cycle she is tested. FSH levels are incr above normal bc of this. Which S/S observed in this pt is a DIRECT consequence of the elevated FSH?
A) Acne
B) Hirsutism
C) Larger than normal follicles
D) Obesity
B) Testosterone
C) Larger than normal follicles (High FSH)
PCOS: due to excess androgen production
94
As a participant in a clinical research study, a normal woman is found to have GnRH pulses every 100 minutes. What other events are likely to be occurring in this woman at the time blood was drawn?
A) The follicle supporting the ovum that will be ovulated this cycle ("chosen one") is growing larger due to the effects of FSH
B) The corpus luteum is secreting large amounts of progesterone in response to hCG
C) CRH produced by placenta-->fetal adrenal gland producing DHEAS-->estrogen secretion and initiation of labor
Pt also experienced signs of excess androgen prod. What organ produces this?
A) The follicle supporting the ovum that will be ovulated this cycle ("chosen one") is growing larger due to the effects of FSH
Follicular phase
Ovary (Follicles)
95
Ultrasound evaluation of the pts ovaries reveal many cysts that are found to be follicles that never ruptured and very few corpora lutea. What even is likely absent in the pts menstrual cycle?
A) Ovulation
B) Ova not entering growth phase
C) Progression of follicles through to the late Antral stage
D) Acquisition of gonadotrope sensitivity by the follicles
A) Ovulation
96
What is the general sequence of steroid synthesis in the ovary?
Cholesterol-->
Progesterone-->
Androgen-->
Estrogen
97
Normal woman shows incr kisspeptin release in response to estrogen production by her ovaries. What other events are occurring at this point in the repro cycle?
```
A) The LH surge
B) Implantation
C) Uterine gland secretion
D) Spinal aa. vasoconstriction
E) Endometrial lining ischemia
```
A) LH surge
Kisspeptin AVPV
98
```
Which of the following functions of a normal fetal liver are functioning at full or nearly full capacity at birth?
A) Synthesis of clotting factors
B) Glycogen storage
C) Gluconeogenesis
D) Drug metab
```
B) Glycogen storage
| and IRON!
99
Fetus experiencing serious hypoxia due to maternal asthma attack. What is occurring?
A) Decreased HR
B) Vasodil of renal vasc
C) Incr HR variability
D) Incr central chemo receptor activation
E) Incr paradoxical breathing
A) Decreased HR
100
Functions for gas exchange, nutrition, and homeostasis
Placenta
Notes: Fulfills role for the lungs, kidney, and GI tract so that the organ can develop the capacity to fill the role in the future--->further development after birth
101
Fetal blood equilibrates w/ mom's blood via simple diffusion...What does this mean for the ion composition of the baby?
Ionic composition of mom=baby's
| ECF mom=baby
102
Fick's law (J): Surface area available for exchg/ diffusion distance.
- Diffusion distance in placenta= 5x what it is in alveoli...THICK
- @ Placenta, maternal PaO2
Dec diffusion of O2 at placenta
Fetal PaO2=30mmHg LOW (HbF's high affinity for O2 overcomes this prob)
103
- Normal CNS development is both genetic and environmental
| - Process of myelination completes at what age?
30 years old!
| myelination of frontal-temporal assoc...judgement
104
TQ
| Motor and sensory systems must develop with the nervous system. Why?
Reciprocal chemical signals are required for synapse formation...
(muscle and nerve develop together)
105
```
Motor development:
Rudimentary reflexes wk 8-->
Chemical feedback-->
Full reflexes wk 12-->
Last trimester-->?
```
- Stereotypical motions (organized patterns)
- mediated at brainstem/midbrain
- ex: turning twd a sound, suckling (not volitional)
- can see some volitional movement
106
Physical development of sense organ (ear) and neuro processing (auditory) develop together.
- Ex: Need ossification of inner ear bones in order to hear
- Neurons actually overdevelop which requires what process? What does this mean for a preemie baby?
Neurons require 'pruning' to dec # of synapses late trimester and post-natally
*Preemie babies can be oversensitive to stimuli bc too many synapses (haven't been pruned yet)
107
EEG:
In the 3rd trimester, we see true wakefullness w/ incr voltage
What do we see in the first 2 trimesters on EEG?
- REM w/ fetal breathing movements
- low voltage, but don't see any true wakefullness (alpha & beta waves)
- slow HR
108
TQ
-Generates intermittent respiratory rhythm
note: respiratory motions ARE REQUIRED for normal growth of lung even though don't occur often
Pre-Botzinger
| of the medullary respiratory center
109
TQ
| What occurs in a congenital diaphragmatic hernia?
- Diaphragm doesn't fuse, lungs cant expand...
| - Underdeveloped lungs bc no respiratory motions
110
TQ
| What are the 2 forms of respiratory motions?
- Paradoxical form (abdominal m. and diaphragm counter each other)
- "Gentle" respiratory motion: during REM is required for lung growth
111
TQ
Fetal lungs are collapsed and airspaces are not complete until when?
What produces the fluid of the fetal lung that contributes to the amniotic fluid?
24-26 wks
CFTR channel
112
Respiratory motions will move limited amount of fluid in and out of a fetal lung and require a high level of work. Why so difficult?
1) High elastin levels (-->low compliance) (collapsed)
2) More negative intrapleural pressure-->
Harder for lungs to expand-->
Decr lung movement
113
TQ
| What does physical growth of the lungs require?
IGF-2 and GH
114
Fetal respiratory control:
- Central chemoRs not fxnl (-->no drive to breathe)
- Peripheral chemoRs fxnl, but don't affect breathing (suppressed respiration
Why does fetus want to suppress respiration if hypoxic?
If fetus is stressed, it shuts down respiratory movements to conserve E (& O2 use) to conserve O2 for elsewhere.
Think of fetal breathing as a 'waste' of E because cant incr PaO2 by breathing.
115
At birth the first breath is a gasp. Why?
- Low lung compliance due to low lung volume (difficult to breathe)
- Easier with each successive breath b/c volume & compliance increases
- ChemoR change to facilitate breathing over several months (SIDS issues)...MechanoR must become LESS inhibitory
116
MechanoRs are strongly inhibitory during the fetal period. How does this affect the fetus?
Shuts off respiratory control ctr during times of hypoxia
After birth, must change chemoR to incr respiratory output of medullary respiratory centers
AND
Make mechanoR LESS inhib!
117
Heart in utero:
| Why do we see a RV hypertrophy but a relative "atrophy" of the LV?
RV:
Hi pulm resistance>>
RV pumps harder>>
Hypertrophy of RV (rvses after birth).
```
LV:
Placenta lowers TPR for fetus>>>
Low vascular Resistance>>
Low BP>>
LV doesn't have to pump very hard>>
'Relative LV atrophy'
```
118
TQ
Where do we see high oxygenation in the fetus?
hint: lowest=SVC
- Liver/portal v. (umbilical v travels 1st)
- Ascending aorta (blood-->brain)
- IVC (where umbilical v. joins)
119
TQ
Patterns of blood flow in utero:
```
IVC: Hi O2 (from placenta)>>
RA>>
Foramen Ovale>>
LA>>
LV>>
Ascending Aorta (to supply brain).
```
What about for the SVC?
```
SVC: Low O2 (from brain)>>
RA>>
RV>>
Pulmonary a.>>
Hi pulm resistance causes blood to go thru Ductus Arteriosus>>
Aorta>>
Umbilical a>>
Placenta
```
120
Blood from the IVC goes preferentially where?
Blood from the SVC is directed to the placenta due to low vascular resistance (lowest O2) (40-65% CO)
heart and head (30% CO)
121
CO is high in utero (low resistance, high volume of placenta + vasodilation of all tissue due to hypoxia)
Most of the CO goes where?
Placenta>>
Brain and heart>>
Lungs and body
122
What controls initial incr in fetal heart rate in response to hypoxia? What happens overtime?
Chemoreceptors initially incr HR but with further hypoxia, slows HR
(no point in pumping faster if all blood is de-O2)
123
What controls HR variability in the fetus?
Autonomics!
| Para/sympathetics are present
124
What is the fetal hypoxemic/ asphyxial response?
Hint: detected by peripheral chemoreceptors
(stress to a fetus is hypoxia/ischemia)
Periph ChemoRs sense hi CO2, low O2, low arterial pH-->
1) Major vasoconstriction to everywhere except heart, brain, & placenta
2) Bradycardia (incr first then slows)
125
- Fetal renal blood flow/g tissue is constant.
- GFR increases through gestation and birth (50-60 ml/min)
- Renal tubular fxn NOT mature until after birth (placenta does all the work).. spills Na, Glucose, and protein into the urine
What does this mean for a baby with dehydration?
```
Limited ability to concentrate urine immediately after birth>>
worsens dehydration (diarrhea)
```
*Limited acid-base compensation immediately after birth
126
- In utero, GI system absorbs glucose & H2O
- Swallowing & peristalsis by 4mo.
Why the limited GI absorptive capability?
No intestinal flora
127
Liver well developed by 5th month.
| Major function of liver in utero?
Glycogen & Fe storage (store for time immediately after birth when don't have milk)
Most other fxns dec in utero (protein syn, gluconeogenesis: mom controls glucose, drug metab)
128
- Fetal thyroxine: earliest to be produced by fetus
- GH-->IGF-2: organ growth (esp lungs)...mannose-6-phosphate R
- Glucocorticoids: stress response
What is inuslin's role?
MAJOR GH of fetus
Tells baby there is food around to grow
129
- Fetal renal blood flow/g tissue is constant.
- GFR increases through gestation and birth (50-60 ml/min)
- Renal tubular fxn NOT mature until after birth (placenta does all the work).. spills Na, Glucose, and protein into the urine
What does this mean for a baby with dehydration?
```
Limited ability to concentrate urine immediately after birth>>
worsens dehydration (diarrhea)
```
*Limited acid-base compensation immediately after birth
130
- In utero, GI system absorbs glucose & H2O
- Swallowing & peristalsis by 4mo.
Why the limited GI absorptive capability?
No intestinal flora
131
Liver well developed by 5th month.
| Major function of liver in utero?
Glycogen & Fe storage (store for time immediately after birth when don't have milk)
Most other fxns dec in utero (protein syn, gluconeogenesis: mom controls glucose, drug metab)
132
- Fetal thyroxine: earliest to be produced by fetus
- GH-->IGF-2: organ growth (esp lungs)...mannose-6-phosphate R
- Glucocorticoids: stress response
What is inuslin's role?
MAJOR GH of fetus
Tells baby there is food around to grow
