Physiology and pathology Flashcards
Primary oocyte
In fetal life–>meiosis I of prophase prior to ovulation
Diploid
What happens to the primary oocyte during Ovulation?
–>Meiosis II in metaphase II until fertilization
Haploid
How long does the oocyte have to fertilization before it degenerates?
1 day
Elevated hormones in ovulation
^estrogen–>^GnRH receptors on anterior pituitary–>^^^surge in LH–>rupture of the follicle
How does a spike in progesterone change basal temperature?
Temperature increases
Mittelschmerz
Transient mid-cycle ovulatory pain (peritoneal irritation) can mimic a appendicitis
Where does fertilization most commonly occur?
Ampulla of the fallopian tube
What secretes hCG?
Syncytiotrophoblasts (also stimulates the corpus luteum to make progesterone during the 1st trimester)
Suckling of the nipple stimulates?
Nerves to increase oxytocin and prolactin
Oxytocin function
Induces labor and stimulates milk let down
Prolactin function
Induces and maintains lactation and decreases reproductive function
What do breastfed infants require in addition?
Vitamin D
Function of the corpus luteum for the first 8-10 weeks?
Produce progesterone, functions as place holder until the placenta is large enough to make its own progesterone/estriol
Elevated hCG is indicative of?
Multiple gestations, hydatidiform moles, choriocarcinomas, Down syndrome
Decreased hCG is indicative of?
Edward, Patau, ectopic/failing pregnancy
What is the specific lab value indicating menopause?
FSH (loss of negative feedback from decreased estrogen)
Menopause before age 40 may indicate?
Premature ovarian failure
What are the hormonal changes associated with menopause?
Decrease in estrogen, Big increase in FSH, increase in LH and GnRH
Menopause symptoms
Menopause wreaks HAVOCS Hot flashes Atrophy of the vagina Osteoporosis Coronary artery disease Sleep disturbances
Where does spermatogenesis occur?
Seminiferous tubules
When does spermatogenesis begin?
At puberty
Spermatogonium ploidy
Diploid 2N, 2C (N=unique genetic content, C=cr)
Primary spermatocyte ploidy
Diploid 2N, 4C
Secondary spermatocyte ploidy
Haploid 1N (X or Y), 2C(XX or YY)
Spermatid ploidy
Haploid 1N, 1C
Mature spermatozoon
Haploid 1N, 1C (loss of cytoplasmic contents and gain of acrosomal cap
Androstenedione produced from?
ADrenals (AnDrostenedione)
Potency of androgens
DHT>testosterone>androstenedione
Main functions of testosterone
In utero: Develops the internal male structures
Puberty: Growth spurt, voice deepening, closing epiphyseal plates, libido
Main functions of DHT
In utero: Differentiation of external male structures
Later stage: Prostate growth, balding, sebaceous secretions
Effects of exogenous testosterone
Inhibitions Hypo-pit-gonadal axis–>decrease in intratestiscular testosterone–>azoospermia
Klinefelter syndrome presentation
Long limbs, testicular atrophy, Dev delay (maybe), female fat distribution/hair growth pattern
Klinefelter genotype and hormone levels
47, XXY
Dysgenesis of seminiferous tubules–>decrease in inhibin–>^FSH
Abnormal leydig function–>decrease in testosterone–>Increase in LH–>increase in estrogen
Turner syndrome genotype and hormone levels
45, XO
Decrease estrogen–>^FSH/LH
Can be monosomy or mosaic
Turner syndrome presentation
Webbed neck, cystic hygroma, shield chest, short stature, steak ovaries, preductal coarctation (Brachial>femoral pulse), bicuspid aortic valve
Rx for pregnancy in Turner syndrome
Oocyte donation with exogenous estradiol-17B and progesterone
Hormone levels in Kallman syndrome
Decreased GnRH, LH, FSH, testosterone–>infertility/amneorrhea
Kallman syndrome presentation
Failure to complete puberty, defect in GnRH cells and formation of olfactory bulb (anosmia)
Aromatase deficiency
Inability for females to synthesize estrogen from androgens–>masculinization of females
Female pseudo-hermaphrodite (XX)
Ovaries present, but external genitalia are virilized or ambiguous
Due to exogenous androgens or congential adrenal hyperplasia
Male pseudo-hermaphrodite (XY)
Testes present, but external genitalia are female
Due to androgen insensitivity syndrome
Testosterone and LH levels in: defective androgen receptor
Increase T and LH
Testosterone and LH levels in: Testosterone-secreting tumor
Increased T and decrease LH
Testosterone and LH levels in: Primary hypogonadism
Decreased T and increased LH
Testosterone and LH levels in: Hypogonadotropic hypogonadism
Decrease T and LH
Hydatidiform mole associated with
Theca-lutein cysts, hyperemesis gravidarum, hyperthyroid
Risk of cancer associated with moles?
2% risk of developed choriocarcinoma in COMPLETE moles
Symptoms of a complete mole
First trimester bleeding, enlarged uterus, hyperemesis, pre-eclampsia, hyperthyroidism
Imaging of a complete mole
Honey combed, grape clusters, snow storm on US
Symptoms of a partial mole
Vaginal bleeding and abdominal pain
Imaging of a partial mole
Fetal parts
Gestational HT presentation
BP>140/90 after 20th week of gestation
No pre-existing HT
No proteinuria or end organ damage
How do you treat gestational HT
Antihypertensives: a-methyldopa, labetalol, hydralazine, nifedipine
Deliver at 37-39 weeks
Preeclampsia presentation
New onset HT with proteinuria or end-organ dysfunction after 20th week of gestation
What are the causes of preeclampsia?
Abnormal placental spiral arteries–>endothelial dysfunction, vasoconstriction and ischemia
Risk factors for preeclampsia
Pre-existing HT, diabetes, chronic renal dz, autoimmune disorders
Don’t give ACE I (renal damage!)
How do you treat preeclampsia?
Antihypertensives, IV magnesium sulfate
Don’t give ACE I (renal damage!)
Eclampsia presentation
Pre-eclampsia with seizures
Can lead to maternal death due to stroke, ICH, ARDS
How do you treat eclampsia?
IV magnesium sulfate, antihypertensives, immediate delivery
HELLP syndrome
Hemolysis Elevated liver enzymes Low platelets A manifestation of severe preeclampsia Blood smear shows shistocytes Can lead to hepatic subcapsular hematomas-->rupture-->severe hypotension
Sheehan syndrome risk factors
No separation of the placenta after delivery–>postpartum bleeding–>necrosis of the anterior pituitary–>hypopituitarism
Polyhydramnios is associated with
Fetal malformations (esophageal duodenal atresia, anencephaly–>can’t swallow fluid), maternal DM, fetal anemia, multiple gestations
Oligohydramnios is associated with
Placental insufficiency, biltaeral renal agenesis, posterior urethral valves (males)–>can’t excrete urine
–>can lead to Potter sequence
Incidence of gynecologic tumor embryology
Endometrial>ovarian>cervical
Prognosis of gynecologic tumors
Ovarian>cervical>endometrial
Sarcoma botryoides
Girls under 4 years
Spindle shaped cells, desmin+
Clear, grape-like polypoid mass emerging from vagina
HPV 16 and 18 inhibit which genes
p53 suppressor gene (due to E6 gene product)
RB supressor gene (due to E7 gene product)
Histology of cervical dysplasia
Koliocytes-wrinkled raisinoid nuclei
May have clearing or perinuclear halo
Patients with polycystic ovarian syndrome are at risk for?
Endometrial cancer
LH and FSH values in PCOS
3:1 LH/FSH–>activation of theca interna cells–>increase in androgens–> decreases the rate of follicular maturation and unruptured follicles become cysts
PCOS presentation
Enlarged bilateral cystic ovaries
Amenorrhea/oligomenorrhea, hirsutism, acne, subfertility
Associated with obesity
Theca-lutein cyst associated with
hydatiform mole and choriocarcinoma
Theca-lutein cyst induced by
gonadotropin stimulation
Follicular cyst induced by
hyperestrogenism, endometrial hyperplasia
How do you monitor progression of Ovarian cancer?
CA-125
Most common ovarian neoplasm
Serous cystadenoma
What is it called when you see hyperthyroidism due to mature teratoma?
Struma ovvarii (functional thyroid tissue in the cyst)
Call-exner bodies are associated with what type of cancer
Granulosa cell tumor
Granulosa cells haphazardly around collections of eosinophilic fluid, looks like primordial follicles
Schiller-Duval bodies are associated with what type of cancer?
Yolk sac tumors
look like glomeruli
Tumor marker associated with dysgerminoma
LDH+
hCG+
(fried egg cell appearance on histology)
Tumor marker associated with yolk sac tumor
AFP+
Leiomyoma
Most common tumor in females (^ in blacks, benign, E sen.)
Histology: whorled pattern of smooth muscle bundles with well demarcated borders
How do you treat endometriosis
Rx. NSAIDs, OCPs, progestins, GnRH agonists, danazol, removal
How do you treat endometritis?
Gentamicin+clindamycin with/without ampicillin
Endometrial hyperplasia puts a patient at risk for?
Endometrial carcinoma
Endometrial hyperplasia is typically caused by?
Elevated estrogen
Endometrial hyperplasia presentation?
Postmenopausal bleeding
Endometrial carcinoma presentation?
Vaginal bleeding (typically proceeded by endometrial hyperplasia)
What is the most common gynecologic malignancy?
Endometrial carcinoma
Endometrial carcinoma risk factors
Prolonged use of estrogen without progestins, obesity, diabetes, HT, nulliparity, later menopause, Lynch syndrome
How do you treat lactational mastitis?
Dicloxacillin and continued breastfeeding
When is male gynecomastia physiologic?
Birth, puberty, old age
Drugs that induce gynecomastia?
Spironolactone, digoxin, cimetidine, alcohol, ketoconazle (seborrheic dermatitis)
Some drugs create awesome knockers
What is the most important prognostic factor in malignant breast cancer?
Spread to the axillary nodes
Risk factors for metastatic breast cancer
Increased estrogen exposure, ^ total number of menstrual cycles, older age at 1st live birth, obesity, BRCA1/BRCA2 mutation, African American ethnicity (increase risk of triple -)
DCIS pathology
Fills ductal lumen, often see microcalcifications on mammography
Comedocarcinoma
Subtype of DCIS with central necrosis
Paget disease of the breast
Underlying DCIS or invasive cancer
Eczematous patches on nipples
Paget cells=large cells in epidermis with clear halo
Orange peel breast skin is associated with?
Inflammatory malignant breast tumors
Invasive ductal carcinoma
Firm, fibrous, rockhard mass, with shape margins with classic stellate infiltration on gross imaging
Invasive ductal carcinoma histology
Small, glandular duct-like cells
Invasive lobular carcinoma histology
Orderly rows of cells due to decreased E-cadherin expression
Medullary breast cancer
Good prognosis
Fleshy, cellular, lymphocytic infiltrate
Peyronie disease
“peyronie, curved like a pony”
fibrous plaque within tunica albuginea
Where does prostatic adenocarcinoma arise
posterior prostate
Where does the prostate most commonly metastasize to?
Bone
Pulsatile leuprolide
GnRH agonist
Continuous leuprolide
GnRH antagonist (decrease in FSH/LH)
Clinical use of leuprolide
Infertility (pulsatile) Prostate cancer (continuous, use with flutamide) Precocious puberty (continuous)
Toxicity of leuprolide
Antiandrogen, nausea, vomitting
Synthetic estrogen clinical use
Female hypogonadism, ovarian failure, menstural abnormalities, hormone replacement therapy,
Can be used in men with androgen-dependent prostate cancer
Synthetic estrogen toxicity
Increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell carcinoma of vagina in females exposed to DES in utero
Increased risk of thrombi
Contraindication in ER+ breast cancer and PH of DVTs
Clomiphene mechanism
SERM: Antagonist at estrogen receptors in hypothalamus
Prevents normal feedback inhibition and increases release of LH and FSH from pituitary–>stimulates ovulation
Clomiphene clinical use
Infertility (PCOS),
Clomiphene toxicity
Hot flashes, ovarian enlargement multiple simultaneous pregnancies, visual disturbances
Tamoxifen mechanism
Antagonist at breast, uterus
Agonist at bone
Tamoxifen clinical use
Use to treat and prevent recurrence of ER/PR+ cancer
Tamoxifen toxicity
Increases risk of thrombolytic events and endometrial cancer
Raloxifene clinical use
Primarily used to treat osteoporosis
Raloxifene toxicity
Increased risk of thromboembolic events but NO increased risk of endometrial cancer (like in tamoxifen)
Raloxifene mechanism
Antagonist at breast, uterus
Agonist at bone
Anastrozole/exemestane
Aromatase inhibitors use to postmenopausal women with ER+ breast cancer
Progestins clinical use
bind progesterone receptors–>Decrease growth and increase vascularization of the endometrium
Progestins clinical use
Oral contraceptives
Endometrial cancer Rx
Abnormal uterine bleeding
Mifepristone mechanism
Competitive inhibitor of progestins at PR
Mifepristone clinical use
Termination of pregnancy
Mifepristone toxicity
Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain
Terbutaline/ritodrine
B2 agonists: relax the uterus to decrease contraction frequency in women during labor
Danazol mechanism
Partial adrogen agonist
Danazol clinical use
Endometriosis, hereditary angioedema
Danazol toxicity
“become like Dan (a man)”
Weight gain, edema, acne, hirsutism, masculinization, decrease HDL levels, hepatotoxicity
Anti androgen names
Finasteride 5a-reductase inhibitor
Flutamide- Non steroidal competitive inhibitor at androgen receptors (prostate carcinoma)
Ketoconazole- Inhibits steroid synthesis
Spironolactone- Inhibits steroid binding
Tamsulosin
A1-antagonist used to treat BPH (also terazosin)
Selevtive a1A,D receptors that are found on the prostate, not on vascular receptors (a1B)
Sildenafil, vardenafil, tadalafil
Inhibits PDE-5–>^cGMP
Smooth muscle relaxation of corpus cavernosum
Increases blood flow to the penis
“FILl the penis”
Sildenafil, vardenafil, tadalafil toxicity
HA, flushing, dyspepsia, cyanopsia (blue tinted vision)
**Risk of life threatening hyptotension in patients taking nitrates
Minoxidil
Androgenetic alopecia, severe refractory hypertension
Direct arteriolar vasodilator
