Physiology and Pathophysiology Flashcards
What are the major functions of the HPO (Hypothalamic Pituitary Ovarian) Axis?
- Development of sexual characteristics
- Coordinating regular periodic body changes (ovarian and uterine cycle)
- Role in cervix, vagina, breast function
- Maintenance of pregnancy
What is the pathway of hormones from the hypothalamus to the ovaries?
Hypothalamus releases GnRH –> anterior pituitary –> LH/FSH –> ovary –> estrogen and progesterone
How is GnRH released from the hypothalamus?
In pulses
What type of cells release LH and FSH?
Gonadotrope cells in the pituitary (FSH and LH then travel to ovary)
What does FSH and LH bind to in the ovary?
Theca and granulosa cells which causes folliculogenesis (maturation of the follicle)
In addition to folliculogenesis, what do FSH and LH stimulate production of in the ovary?
- Steroid hormones: estrogens, progesterone, androgens
- Gonadal peptides: activins, inhibins, follistatins
- Growth factors
What are the functions of estrogens?
- Induce surge of LH causing oocyte release
- Encourage proliferation of endometrium, myometrium
- Development of secondary sex characteristics
- Libido
- Thicken vaginal wall and increase lubrication
- Reduce acne
- Reduce cholesterol and atherosclerosis
Secondary sex characteristics: breast enlargement and areolar pigmentation, mature female body shape, increased scalp hair, less body hair
What are the roles of progesterone?
- Maintenance of pregnancy
- Decrease uterine contractility
- Breast development and differentiation
- Falling progesterone triggers menses and signals lactation after pregnancy
What is the role of activins?
- Stimulate FSH secretion
- WBC production and embryo development
What is the function of inhibins?
Inhibit FSH secretion
What is the role of follistatins?
- Regulate gonadotropin secretion
- Bind to and inhibits activins
What is the role of relaxin?
- Relaxes pubic symphysis, other pelvic joints in pregnancy
- Inhibits uterine contractions
- May help mammary gland and follicular development and ovulation
What are positive feedback mechanisms associated with the normal HPO axis?
- High estrogen –> increased GnRH and LH
- Activin promotes gonadotropin cell function
What are negative feedback mechanisms associated with the normal HPO
- Progesterone inhibits GnRH and LH
- Inhibin inhibits FSH
- Follistatin inhibits FSH
- Lactation –> hyperprolactinemia causes increased dopamine and altered release of GnRH
- Estrogen decreases LH
- Estrogen decreases FSH
What are examples of pathologic HPO axis feedback?
- Hypogonadism
- PCOS
- hyperprolactinemia
- Medications: steroids, hormones, opioids
- Weight status (obesity = higher estrogen)
What is the usual age for puberty?
- 8-13 F, 9-14 M
What factors influence the 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
- Estradiol duct growth
- Progesterone lobule and alveoli growth
What is pubarche?
Development of pubic and axillary hair, which is second event of puberty in females
What is menarche?
First menstrual cycle
Typically anovulatory for first 12-18 months
How long does the average menstrual cycle last? How long is the flow? What is the average blood loss?
- 28 days (+/- 7 days)
- Flow- 3-5 days
- Average blood loss of 30 mL
How long are menstrual cycles irregular?
- 1-2 years after menarche
- 2-3 years preceding menopause
What are the 2 cycles that are part of the menstrual cycle?
Ovarian and uterine cycle
What are the phases of the ovarian cycle?
Follicular phase –> ovulation –> luteal phase
What are the phases of the uterine cycle?
- Proliferative phase
- Secretory phase
- Menses
What happens during the preovulatory phase of the follicular phase of the ovarian cycle?
- Rise in FSH > LH early in cycle
- Several follicles enlarge
- FSH causes production of inhibin B which decreases FSH release later in follicular phase
What is the midfollicular phase of the ovarian cycle?
- Day 6
- 1 follicule grows rapidly, becoming dominant follicle
- Other follicles become atretic
What happens after the midfollicular phase of the follicular phase of the ovarian cycle?
Dominant follicle matures, develops LH receptors, and releases estrogens
* Rising estrogen levels –> increased GnRH pulses –> LH surge –> ovulation
What happens during ovulation?
- About day 14
- Mature follicle ruptures
- Ovum is extruded into abdominal cavity and transported into oviduct
- Ruptured follicle fills with blood (corpus hemorrhagicum)
- Mittelschmerz may occur
What happens during the luteal phase of the ovarian cycle?
- About 14 days post ovulation
- Corpus luteum forms
- If pregnancy does not occur, decline in FSH and LH –> atrophy of corpus luteum 3-4 days before menses (eventually becomes corpus albicans)
- Declining levels of progesterone –> shedding of endometrial lining (menses)
What is the corpus luteum?
- Granulosa and theca cells of follicle lining proliferate post ovulation in luteal phase 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
What happens during the preovulatory part of the Proliferative phase of the uterine cycle?
- At end of menses, all but stratum basale is sloughed
What happens during days 5-16 of the uterine cycle?
- Estrogen from developing follicles –> endometrium regenerates from stratum basale to form stratum functionale (outer 2/3)
- Uterine glands lengthen but do not become convoluted or secrete anything
How long is the postovulatory phase of the uterine cycle?
14 days
What happens during the secretory phase of the uterine cycle?
- Postovulatory
- Estrogen and progesterone from corpus luteum cause endometrium to become more vascularized and edematous
- Glands coil and secrete clear fluid
- Corpus luteum regresses –> estrogen and progesterone decline –> vascular spasms –> endometrial ischemia
What happens as the endometrium becomes ischemic during the secretory phase of the uterine cycle?
- Breakdown of extracellular matrix of strata functionalis and necrosis of endometrium and supplying arterial walls
- Causes hemorrhage which coalesces into menstrual flow
What happens to the cervix during the menstrual cycle?
- Cervical mucus has cyclic changes
- Estrogen and progesterone change mucus
What does cervical mucus do with greater quantities of estrogen?
- Thinner and more alkaline to enhance survival of sperm
- Dries in fern-like pattern
Around time of ovulation (day 14)
How does cervical mucus change with greater progesterone?
- Mucus is more thick, tenacious, cellular
- Thickest around day 21 and continuing if pregnancy
- No fern pattern on slide
How will a slide look if a patient undergoes an anovulatory cycle with estrogen present?
Complete ferning (vs partial ferning with ovulation since some progesterone still present)
How does the cervix change during puberty?
- Columnar epithelium extends from endocervix to ectocervix
- Estrogen rises in puberty, cervical os opens to expose endocervix columnar epithelium causing squamous metaplasia during 20s-30s
Acidic environment of vagina causes metaplasia
What can impact cervical metaplasia?
- OCP can cause persistence or reappearance of ectopy
- Smoking accelerates metaplasia
Why is it important to know about cervical ectopy?
- Can mimic infectious endocervicitis
- May increase susceptibility to STIs (columnar is more vulnerable than squamous)
What are the changes in the fallopian tubes that occur due to hormones?
- Progesterone reduces ciliary beat frequency
- Estrogen increases ciliary beat frequency
What are the impacts of female hormones on muscle?
- 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
What are impacts of ovarian hormones on skin?
- Maintains skin collagen and moisture
- Increases cutaneous wound healing and hair growth
- Increases skin pigmentation
What are impacts of ovarian hormones on fat deposition?
- Increase fat deposition for “pear shape”
- Progesterone- mediator of fat gain in pregnancy
What are impacts of ovarian hormones on sodium/water balance?
- Estrogen- sodium and water retention
- Progesterone- sodium and water excretion
What are cardiovascular changes during pregnancy?
- PMI shifts laterally
- Heart size increases 12%
- Increase in myocardial mass and intracardiac volume
- Supine hypotensive syndrome can occur
- Stroke volume increases
- HR increases
- CO increases
- BP decreases slighly with LE venous pressure increasing
- PVR decreases
- Blood flow distribution increases to uterus, kidneys, breasts, and skin
What are signs/symptoms of supine hypotensive syndrome?
- Hypotension
- Bradycardia
- Syncope
How is supine hypotensive syndrome treated?
R or L recumbent position
What could cause a greater increase in stroke volume during pregnancy?
Maternal position and multiple gestation
How much does pregnancy impact HR? What other factors can impact maternal HR?
- 15 bpm more at term than nonpregnant rate, progressively increasing throughout pregnancy
- Exercise, stress, heat, meds
- Multiple gestation
What causes CO increase during pregnancy?
- Hormonal changes, shunt of uteroplacental circulation
- Transient increase during L&D
How does blood pressure change during pregnancy?
- Arterial pressure declines slightly and returns to prepregnancy levels at 36 weeks
- Widened pulse pressure
- LE venous pressure progressively increases –> edema and varicosities
How does peripheral vascular resistance change during pregnancy?
- Decreases due to enhanced vasodilators
- At delivery 40% decrease in vascular resistance, offset by rise in CO
What can strenuous exercise do to blood flow distribution during pregnancy?
Divert blood
What are changes that occur in heart sounds and murmurs during pregnancy?
Heart sounds and murmurs: Systolic murmurs (up to 90%)
* May see split S1 or loud S3
* Murmurs or bruits at left sternal edge d/t increased blood flow through internal thoracic (maternal) artery
What are changes to heart rhythm during pregnancy?
- Decreased threshold for reentrant SVT
- May see sinus tachy, sinus brady, isolated PAC/PVCs
What are common changes to EKG during pregnancy?
- Left axis shift
- ST depression
- T-wave flattening
What are respiratory anatomy changes during pregnancy?
- Capillary dilation: engorged nasopharynx, larynx, trachea, bronchi–> may see prominent pulmonary vascular markings on CXR
- Rib cage increasingly displaced upward with elevated diaphragm and increased thoracic circumference