Physiology

Question 1

adrenarche

Answer 1

regeneration of zone reticularis in adrenal cortex and production of androgens -> pubic hair

age 6 and 8

growth primary 2/2 sex steroids and growth hormone

Question 2

Gonadarche

Answer 2

activation of hypothalamic pituitary goal axis’s -> pulsatile GnRH and FSH and LH

independent of adrenarche and starts age 8

Question 3

thelarche

Answer 3

breast development - 1st sign around age 10

Question 4

pubarche

Answer 4

pubic and auxiliary hair development - age 11. follows thelarche usually

Question 5

Menarche

Answer 5

menstruation onset, age 12-13, 2.5 yrs after breast development

irregular first 1-2 yrs

Question 6

precocious puberty

Answer 6

puberty before 7 in white girls 6 in black ;

delayed after 12yrs

Question 7

Menstrual cycle

Answer 7

2 14 dya periods
Follicular phase- release of FSH from pituitary -> ovarian follicle (makes estrogen), uterine lining proliferates, LH spike responds to estrogen -> Ovulations

Luteal phase- remnant follicle -> corpus luteum, secretes progesterone and maintains endometrial lining

Question 8

Tanner stages 1-5

Answer 8

1 elv papilla only

2. elv of breast and papilla, areolar deve
3. enlargement
4. Projection of areola and pail
5. Maturity

Question 9

Follicular phase

Answer 9

less estrogen and progesterone-> FSH, stimulates 5-15 ovarian follicles -> dominant

Theca interna cells-> androstenedione in response to LH
Granulosa cells -> convert androstenedione to estradiol

Estrogen feedback on FSH

Question 10

Ovulation

Answer 10

estrogen level -> anterior pituitary to release LH spike -> resumption of meiosis and production of progesterone, release, moves into fallopian tube

process takes 3-4 days to

fertilization must occur w/in 24 hrs

Question 11

Luteal phase

Answer 11

granulosa and theca cells form corpus luteum => estrogen and progesterone -> enfometrium becomes glandular

Fertilization -> Trophoblast synthesizes human chorionic gonadotropin (similar to LH), maintains corpus luteum; maintained for 8-10 wks till placenta

Question 12

Perimenopause

Answer 12

irregular menstrual cycles, hot flashes, night sweats, mood swings,

inhibin B from ganulosa cells falls-> FSH rises

estradiol preserved until late perimenopause and FSH and estradiol fluctuate

Question 13

menopause

Answer 13

12 months of amenorrhea after final menstruation period, nearly all oocytes undergone atresia -> symptoms for 1-2 yrs

avg age 51,
5% late >55,
5% early (40-45) - smokers, short cycles, null parity, T1DM,

Question 14

Symptoms of menopause

Answer 14

ages 48-52
amenorrhea, vasomotor instability, sweats, mood changes, depression, dyspareunia, dysuria, atrophy of breasts, vaginal, urethra, cervix, w decreased estrogen levels

FSH >40( amenorrhea or oligomenorrhea and menopause)

disappear in 1-2 yrs but can go on for 5

Question 15

2 long term consequences of menopause

Answer 15

cardioprotective element of estrogen on lipids and vascular endothelium (prevents athrogenesis, inhibits platelet adherence) is LOST

Bone reabsorbtion accelerates w/ estrogen regulating osteoblast-> osteopenia (lose 20% of density in 1st 5-7 yrs)

Question 16

Osteoperosis risk factors

Answer 16

weigh

Question 17

Role of hormone replacement therapy and estrogen therapy

Answer 17

Unopposed estrogen -> endometrial hyperplasia and possible CA, progestine must be used to decrease risk; if hystorectomy there is no risk

Benefit: control menopausal symptoms(fluching, mood, sleep, atrophy, skin and muscle tone, were colon CA and fxr risk)

Risk: Increase DVTs, PE and strokes and invasive breast CA in HRT if used >5y
- estrogen only increase risk of stroke/DVTs but NOT heart attacks and not as much breast CA

Question 18

Contraindications to hormone replacement CA

Answer 18

Chronic liver impairment, pregnancy, estrogen dependent neoplasm (breast, ovary, uterus), Hx of thromboembolic disease, undiagnosed vaginal bleeding

Question 19

Alternatives to HRT for menopause

Answer 19

Vasomotor - clonidine, SSRIs, low doe gabapentin

Vaginal/uterine atrophy: lubes and moisterizers, low dose vaginal estrogen

Osteoperosis- CA and Vit D supplementation, bisphosphonates, clacitonin, raloxifene, tamoxifen, Weight bearing exercises and less smoking/alcohol

Question 20

Alternatives to HRT for menopause

Answer 20

Vasomotor - clonidine, SSRIs, low doe gabapentin

Vaginal/uterine atrophy: lubes and moisterizers, low dose vaginal estrogen

Osteoperosis- CA and Vit D supplementation, bisphosphonates, clacitonin, raloxifene, tamoxifen, Weight bearing exercises and less smoking/alcohol

Question 21

Pubertal sequence

Answer 21

accel growth, Breast dev, pubic hair, menstruation

variation in AA is pubarche before thelarche

Question 22

Breast anatomy

Answer 22

Supported by cooper suspensory ligaments

Main blood supply- internal mammary and lateral thoracic arteries

axillary lymph nodes drain 97%-> internal mammary nodes responsible for 3% and drain UIQ and LIQ

intercostobrachial nerve innervation supplies upper medial arm and long thoracic nerve (C567, innrevates serratus anterior; throcaodorsal nerve innervates latissmus dorsi

Question 23

Hormones in breasts

Answer 23

estrogen-> ductal development and fat deposition
Progesterone -> lobular-alveolar stroma development (lactation possible)
oxytocin- milk let down
prolactin - milk production

Question 24

Breast CA screening

Answer 24

breast self exams >20y are optional -> breast awareness
Clinical breast eval 1-3 yrs for age >20
Screening mamography starting 40 50 w/biannual occurrence

no upper age limit

Question 25

High risk Breast CA

Answer 25

BRCA1 or BRCA2. 1st degree relative w/ mutation, chest radiation ages 10-30, Hereditary syndrome: Li fraumeni, Lynch II; moderate risk - personal Hx of breast CA, mammography 5-10 yrs earlier than youngest Dx

Question 26

Breast pain- mastalgia, mastodynia

Answer 26

common complain, mild and 67% cyclic response to hormone fluctiations or response to trauma-> 1-7% have malignancy HX key: cyclic? bilateral?, ICP? fever? trauma, radiation, surgery, breastfeeding, focal trauma lesions can be eval US. high risk mammography. Tx: oral or topical NSAIDs, supprotive bram diet (less caffine and smoking), warm and coll compresses Danazol only FDA Rx but SFx

Question 27

Nipple D/c

Answer 27

50-80% of women- only 5% malignancy | concern w/? spontaneous, bloody, unilateral(bilateral fine), persistent from single duct and assoc mass

Question 28

Most common bloody nipple d/c?

Answer 28

intraductal papilloma, can be papillary CA

Question 29

Galactorrhea assoc w/?

Answer 29

pregnancy, pituitary adenomas, hypothyroidsim, stress, Meds: OCPs, antihypertensives, psych drugs

Question 30

Serous nipple D.c associtated w?

Answer 30

normal menses, OCPs, fibrocystic change, early pregnancy

Question 31

yellow tinged nipple d/c

Answer 31

fibrocystic changes or galactocele

Question 32

Purulent d/c from nipple

Answer 32

superficial or central breast abscess

Question 33

Eval of breast d/c

Answer 33

color, location, skin changes, guaic and cyto eval, prolactin, thyroid. if mass- US or mammo depending on age > or

Question 34

Eval of breast mass

Answer 34

Hx + exam- 10-15% CA not seen on mammography Common: fibroadenomas and breast cysts Worry- dominant, discrete, dense, single, firm, nontender, immobile w/ irregular borders US30 mammography(Bi-rads)

Question 35

BI-RADS classification

Answer 35

mammography eval - spiculated mass, achitectural distortion w/ retraction, asymmetric localized fibrosis, microcalcifications w/ linear branched pattern, vascularity 0-incomplete, 1-negative(routine), 2-benign(routine), 3- prob benign(6m f/u), 4-malig?(core-neeedle), 5-suspicious(core-needle), 6- known

Question 36

Cyst vs solid eval in breast mass

Answer 36

needle aspiration but if bloody/persistent(reaccumulates 2x or re accumulates w/in 2wks) then excise the cyst If palpable solid mass- a tissue sample should be obtained- 30 get core needle biopsy Nonpalpable lesion - exisional biopsy under needle or wire guidance- get 1cm margin

Question 37

Fibrocystic changes of breast

Answer 37

exaggerated stromal response, painful masses that are mtpl and bilateral. NO increased CA risk Ages 30-40 Dx: more pain during premenstual part of cycle T: avoid caffeine, tea and chocolate, Avoid truama, supportive bra, possibly prirose oil, Vit E and B6, danazol, prgestins, bromocriptine, tamoxifen

Question 38

Fibroadenoam

Answer 38

usually solitary, masses larg 1-5cm and usually in women 15035. rare after menopause. rubbery and nontender. May change w/ OCP, cycles and pregnancy Tx:

Question 39

Cystosarcoma phyllodes

Answer 39

rare variant of fibroadenoma, involves epithelial an dstromal proliferation usually premenopausal but can occur at any age Dx: large bulky mobile painless mass (4-7cm). rapid growth and ost lesions are benign. Get core-needle biopsy b/c low-grade malignancy is contained 10%. . Di wide local excision but high rate of local recurrence

Question 40

intraductal papilloma

Answer 40

benign solitary lesion that involves epithelial lining of laciferous ducts most common cause of bloody nipple discharge Dx: bloody nipple d/c in premenopausal - serosanguineous d/c sent for cytology to r/o invasive papillary carcinoma(similar symptoms 25%) Tx: excision of involved duct after localization

Question 41

mammary duct ectasia - plasma cell mastitis

Answer 41

subacute inflam and fibrosis of ductal system causing dialated mammry ducts. Infiltrative cells and periductal inflammation Epidem- at or after menopause - most common Dx: nipple d/c, noncyclic breast pain, nipple retraction, sunareolar mases. D/c is multicolored, sticky, originating from mtpl ducts and often bilateral, mamogram and excsional biopsy r/o of carcinoma Tx: Local excision

Question 42

Risk for breast CA

Answer 42

1st degree FHx, personal Hx, BRCA 1 and 2 (bilateral), ionizing radiation (hodgkin Tx-; atypical ductal or lobular hyperplasia on biopsy. Lifetime estrogen exposure: early menarche, nullparity, late meno; +/- HRT, Past adn current OCP use has not been shown to increase risk Pregnancy or lactation has more Dx surrounding but rates the same and survial rates equivalent Prevent: Early preg, prolonged lactation, chem/surg sterilization, exercise, abstinence from alcohol, low fat diet, phytoestrogens,

Question 43

Tamoxifen MOA

Answer 43

SERM; competitively inhibits estrogen binding and blocks estrogen stim to the breast. ajunt therapy in early stage, surgically treated, ER + breast CA

Question 44

Dx of malignant breast CA

Answer 44

breast awareness, clinical breast exam, mammogram for women age > 40 at high risk. Clinically- breast masses, skin changes, nipple discharge, or symptoms of metastatic disease. Skin dimpling, erythematous, retraction, pleu d'orange Bloody d/c - needs to r/o infasive papillary carcinoma though more commonlu intraductal papilloma 50% of masses in UOQ, can be multifocal, multicentric, or bilateral. Mammography key but does not find 20%, biopsy if suspicious

Question 45

Breast CA mets to

Answer 45

bone, liver, lung, pleura, brain, lymph nodes

Question 46

Lobular carcinoma in situ

Answer 46

proliferation of malignant epithelial cells, bilateral 50%-90%, usually multicentric LCIS-> subsequent risk of invasive CA. Dx is incidental, not palpable and NOT seen on mammograms Tx: observation w/o therapy or chemoprevention w/ SERM or bilateral mastectomy (ipsilateral or contralateral risk)

Question 47

Ductal carcinoma in situ

Answer 47

DCIS - intraductal carcinoma- proliferation of malignant epithelial cells on mammary ducts w/p spread to breast stroma More common than LCIS and has higher tpotnial to progress to invasive carcinoma Age-mid 50s, 90% of DCIS is detected by screening mammography revealing clustered microcalcifications. 10% have palpable mass. 35% multicentric, RARE bilateral Tx: excision of all microcalcifications w/ wide margins. Simplemastectomu for extensive lesions. Radiation therapy if margins inadequate

Question 48

Infiltrating ductal carcinoma

Answer 48

most common breast malignancy, 76% of all invasive breast CA. Tumor arises from ductal epitheliam and infiltrates -

Question 49

Invasive lobular carcinoma

Answer 49

carcinoma arising from the lobular epithelium and infiltrates breast stroma accounts for 8% CA. tends to be bilateral

Question 50

Pagets disease of the nipple

Answer 50

1-3% of breast malignancies. Concomitant w/ DCIS or invasive carcinoma malignant cells enter epidermis of the mipple -> eczematous changes See: crusting scaling, erosion, d/c and maybe breast mass

Question 51

Inflammatory breast Carcinoma

Answer 51

extremely aggressive- 0.5-2% poorly differentiated, dermal lymphatic invasion Symptoms - edema, erythema, warmth, diffuse induration (pleau d'orange) Axillary LAD and distant mets on presentation 17%-36%

Question 52

Invasive breast CA Tx

Answer 52

surgical resection for all invasive, usually breast conserving therapy (BCT)/lumpectomy w/ radiation or modified radical masectomy -> equal survival rates, choice depends on size and histology(large tumors and those that spread lymph node tend to recur more -BCT not recommended) axillary node status key- sentinal node biopsy 1st if positive then lymph node dissection radiation therapy for all Pts w/ conservative therapy - pervent recurrrence(>4 + nodes, large primary tumor, positive resection margins, extracap nodal resection) chemo based on lymph node status + node get chemo, - but high risk >1cm or high tumor grade get chemo: Cyclophosphamide , methotrexate, 5 fluorourcil hormone therapy based on status- tamoxifen, fulvestant

Question 53

Receptor and HER2/neu status in breast Ca

Answer 53

estrogen and progesterone receptor + tumors are well differentiates and less aggressive and favorable prognosis HER2/neu more aggressive

Question 54

systemic adjutant hormone therapy options for breast CA

Answer 54

Tamoxifen - positive ER +/- PR status - antiestrogen, inhibiting binding; 1st line postsurgical Tx for premenopausal breast CA and 2nd line after aromatase inhibitors for postmenopausal Fulvestant - new ER antogonist w/ no agonist activity- Aromatase inhibitors (letrozole, anstozole, exemtane) - for postmeno and receptor positive. new agents have antiesrogenic properties as well HER2/neu status also prognostic- monoclonal antibodies such as trastuzumab for adjuvant Tx (binds)

Question 55

Tx of metastatic/recurrent breast CA

Answer 55

ER negative - combination including: Adricamycin, vincristine in addition to CMF ER positive- pre menopausal - oophorectomu or GnRH antogonists while postmeno Tx w/ tamoxifen or aromatase inhibitors

Question 56

F/u for breast CA Tx:

Answer 56

PE every 3-6 m for 3y; 6-12m for years 4 and 5 breast conservative -> f/u mammogram w/in 6monts mastectomy should have yearly mammograms clinical monitoring for METs Tamoxifen should be followed for irregular bleeding given risk of endometrial CA. biopsy should ne performed No concern of OCPs after w. estrogen. no dif in pegnant women after breast CA Tx, No HRT