Physiology and Pathophysiology Flashcards
Major Functions of the HPO Axis
Hypothalamic-Pituitary-Ovarian Axis
- Development of sexual characteristics
- Coordinating regular periodic body changes
- Ovarian Cycle
- Uterine Cycle - Plays a role in cervix, vagina, breast function
- Maintenance of pregnancy
where is Gonadotropin Releasing Hormone (GnRH)
made?
Hypothalamus
Pathophys of the HPO axis
- Hypothalamus
- Makes and releases GnRH in pulses
- GnRH binds to anterior pituitary gland - Pituitary
- Gonadotrope cells - synthesize and release: Follicle Stimulating Hormone (FSH) & Luteinizing Hormone (LH)
- FSH and LH travel to ovary - Ovary
- FSH and LH
— theca and granulosa cells = folliculogenesis
Besides folliculogenesis, FSH and LH also stimulate ovarian production of:
- steroid hormones
- estrogens, progesterone, androgens - gonadal peptides
- activins, inhibins, follistatins - growth factors
Role/effect of estrogen
- Induces surge of LH = oocyte release
- Encourages proliferation of endometrium, myometrium
-
secondary sex characteristics
- breast enlargement and areolar pigmentation
- mature female body shape
- increased scalp hair, less body hair - Assist with libido
- Thickens vaginal wall and increases vaginal lubrication
- Other effects:
- Reduced acne formation
- Reduced cholesterol, atherosclerosis
Role/effect of progesterones
- Major in maintenance of pregnancy
- Decreases uterine contractility
- Promotes breast development and differentiation
- Falling progesterone levels trigger menses
- Falling progesterone levels after pregnancy signal lactation
What hormone of the HPO axis:
- Stimulate FSH secretion
- Involved in WBC production, embryo development
Activins
Which hormone of the HPO axis inhibit FSH secretion
Inhibins
which hormone of the HPO axis
Help regulate gonadotropin secretion
Binds to and inhibits activins
Follistatins
which hormone of the HPO axis
Relaxes pubic symphysis, other pelvic joints in pregnancy
Inhibits uterine contractions
May help mammary gland and follicular
development and ovulation
Relaxin
what is the normal HPO axis positive feedback?
- Estrogen (high levels) → increased GnRH and LH
- Activin → promotes gondadotropic cell function
what is the normal HPO axis negative feedback
- Progesterone → inhibits GnRH and LH
- Inhibin → inhibits FSH secretion
- Follistatin → inhibits FSH secretion
- Lactation → hyperprolactinemia causes increased dopamine and altered release of GnRH
- Estrogen (prolonged moderate levels) → decreases LH
- Estrogen → decreases FSH
What may affect Pathologic HPO Axis Feedback
- Hypogonadism
- Polycystic ovarian syndrome (PCOS)
- Hyperprolactinemia
- Medications - Steroids, Hormones, Opioids
- Weight status
puberty starts at what age?
ages 8-13 F, 9-14 M
Factors that influence onset of puberty
- Weight and nutritional status
- Genetic factors
- Abnormal hormone levels
what is Adrenarche
increase in secretion of adrenal androgens, DHEA - prior to or at onset of puberty
what is Thelarche
breast development
First event of puberty in females
what hormones play a part of thelarche?
- Estradiol (estrogen) - duct growth
- Progesterone - lobule and alveoli growth
what is Pubarche
development of pubic and axillary hair
Second event of puberty in females
what is menarche?
first menstrual cycle
Typically anovulatory for first 12-18 monhs
Normal Menstrual Cycle lasts how long?
Lasts roughly 28 days (+/- 7 days)
Flow - about 3-5 days
Day 1 of the menstrual cycle is considered when?
1st day of menstruation
not signs of PMS!
when can menstrual cycles be irregular?
- ~ 1-2 years after menarche
- ~ 2-3 years preceding menopause
What are the two major physiologic changes of the menstrual cycle?
- Ovarian Cycle: Follicular Phase → Ovulation → Luteal Phase
- Uterine Cycle: Proliferative Phase → Secretory Phase → Menses
Describe the preovulatory phase
varying length
- Early in cycle - rise in FSH > rise in LH
- Several follicles begin to enlarge
- FSH causes production of inhibin B
— inhibin B decreases release of FSH later in follicular phase
what happens during the Midfollicular phase
about day 6
1 follicle grows very rapidly, becoming dominant follicle
Other follicles regress to become atretic follicles
What happens during the follicular phase?
- preovulatory phase
- midfollocular phase
- As dominant follicle matures…
- Develops LH receptors
- Releases estrogens - Rising estrogen levels → increased GnRH pulses → LH surge → ovulation
what happens during ovulation during the ovarian cycle?
- Midcycle - approximately day 14
- Mature follicle ruptures
- Ovum → extruded in abdominal cavity → transported into oviduct - Corpus hemorrhagicum - ruptured follicle fills with blood
- Mittelschmerz may occur
What happens during the luteal phase of the ovarian cycle?
- Postovulatory - 14 days
- Corpus Luteum - granulosa and theca cells of follicle lining proliferate to form yellowish, lipid-rich luteal cells
- Reacts to LH by making progesterone and estrogen
- Rising levels of estrogen and progesterone → negative feedback → decline in FSH and LH - If pregnancy does not occur → decline in FSH and LH → atrophy of corpus luteum 3-4 days before menses
- Eventually becomes atrophic Corpus Albicans - Declining levels of progesterone → shedding of endometrial lining (menses)
what happens during the proliferative phase of the uterine cycle
- Preovulatory - varying length
- At end of menses, all but the deep layer of the endometrium has sloughed - stratum basale - Days 5-16
- Estrogen from developing follicles → endometrium regenerates from deep layer
- Forms the stratum functionale (outer ⅔)
- Uterine glands lengthen but do not become convoluted or secrete anything
What happens during the sectoary phase of the uterine cycle
- Postovulatory - 14 days
- Estrogen and progesterone from corpus luteum → endometrium becomes more vascularized, edematous
- Glands become coiled, tortuous and secrete clear fluid -
Corpus luteum regresses → estrogen and progesterone decline → vascular spasms → endometrial ischemia
- Breakdown of extracellular matrix of strata functionalis and necrosis of endometrium and supplying arterial walls
- Causes hemorrhage which coalesces into menstrual flow
The 3 phases of the ovarian cycle
- follicular phase
- ovulation
- luteal phase
2 Phases of the uterine cycle
- proliferative phase
- secretory phase
what are the cervical changes during the menstrual cycle?
- Cervix responds differently from uterine body
- No cyclic shedding of lining
- Cervical mucus undergoes cyclic changes - Estrogen → mucus is thinner, more alkaline
- Enhances survival and transport of sperm
- Dries in a fern-like pattern when spread on a slide - Progesterone → mucus is more thick, tenacious, cellular
- NO fern pattern - Cervical Ectopy - Columnar epithelium extends from endocervix to ectocervix
- As estrogen levels rise in puberty, cervical os opens exposing endocervical columnar epithelium
- Squamous metaplasia gradually replaces in 20s-30s due to acidic environment of vagina
When is the cervical mucus its thinnest during the menstrual cycle?
Thinnest at time of ovulation
when is the cervical mucus its thickest during the menstrual cycle?
thickest after ovulation and during pregnancy
What can cause persistence or
reappearance of cervical ectopy
OCP
What may accelerate squamous metaplasia
cervical ectopy
Smoking
Cervical ectopy can mimic what other condition?
infectious endocervicitis
Cervical ectopy may increase the susceptibility to what other diseases?
STIs
What hormones affect the fallopian tubes and what do they do?
- Progesterone - reduces ciliary beat frequency (CBF)
- Estrogen - increases ciliary beat frequency (CBF)
what ovarian hormones affect muscles and what do they do?
- Progesterone - reduces spasms, relaxes smooth muscle, and antagonizes effects of insulin on glucose metabolism
- Estrogen - improves skeletal muscle contractility
- Both estrogen and progesterone may help regulate
- protein metabolism
how do ovarian hormones affect skin?
- Maintains skin collagen and skin moisture
- Increased cutaneous wound healing and hair growth
- Increases skin pigmentation
How do ovarian hormones affect fat deposition?
- Increase fat deposition - “pear shape”
- Progesterone - mediator of fat gain in pregnancy
how do ovarian hormones affect sodium/water balance?
- Estrogen - sodium and water retention
- Progesterone - sodium and water excretion
what are the anatomic CV changes seen in matneral changes?
- PMI shifts laterally
- Heart size increases 12%
- Increase in myocardial mass and
intracardiac volume
what is Supine Hypotensive Syndrome and how to tx?
- hypotension, bradycardia, syncope
- Compression of the vena cava
- Tx - R or L recumbent position
how do maternal changes affect stroke volume?
increases
sensitive to maternal position
increases even more with multiple gestation
how do maternal changes affect HR?
increases
- progressively increases over the course of gestation
- ~ 15 bpm more at term than nonpregnant rate
- still affected by factors like exercise, stress, heat, meds
- increases more in multiple gestation
how do maternal changes affect CO?
increases
- due to hormonal changes, shunt of uteroplacental circulation
- also transiently increases during L&D
how do maternal changes affect BP?
- Arterial pressure declines slightly
- Returns to prepregnancy levels ~36 wks
- Widened pulse pressure - LE venous pressure progressively increases
- Can cause edema and varicosities
how do maternal changes affect peripheral vasular resistance?
- Decreases due to enhanced vasodilators
- At delivery - 40% decrease in vascular resistance
- Offset by rise in CO
how do maternal changes affect blood flow distribution
- Increased to uterus, kidneys, breasts and skin
- Uterus - 4x of normal - Strenuous exercise - may divert blood
how do maternal changes affect Heart Sounds and Murmurs
- Systolic murmurs in up to 90%
- May see split S1 or loud S3
- Murmurs or bruits at left sternal edge
- internal thoracic (mammary) artery
how do maternal changes affect heart rhythm
- Decreased threshold for reentrant SVT
- May see sinus tachy, sinus brady, isolated PAC/PVCs
how do maternal changes affect EKG?
May see L axis shift, ST depression, T-wave flattening
how do maternal changes affect respiratory anatomy?
- Capillary dilation - engorged nasopharynx, larynx, trachea, bronchi
- May see prominent pulmonary vascular
markings on CXR - Rib cage is increasingly displaced upward
- Elevated diaphragm
- Increased thoracic circumference
how do maternal changes affect lung volumes and capacities?
Net Effect - less overall lung space, but less “dead space” and increased tidal volume
how do maternal changes affect respiration?
- More diaphragm-dependent
- Little effect on respiratory rate
- 50% increase in minute ventilation
- Increased arterial O2 and O2 consumption
- Mild respiratory alkalosis
how do maternal changes affect renal anatomy?
- Increased renal size
- Dilated renal calyces and pelves
- Dilated and tortuous ureters
- Bladder - displaced upward,
- flattened, decreased tone - Capacity increased up to 1500 mL