Unit 3 - Chapter 25 Alterations of female reproductive sys

Question 1

Common abnormalities

Answer 1

• uterine agenesis (strucutral malformations) of vagina, uterus, fallopian tubes

Question 2

precocious puberty

Answer 2

• onset (before usual age of 8-13)
• average age of puberty occurring earlier than previous generations
• more common in girls
• caused by mistiming of stimulatory surge in child who HPG system is otherwise normal
• younger pubertal age => obesity
• can be complete (sex appropriate)
  1) lethal CNS tumor may be cause
• **mixed **(not sex appropriate - develop 2ndary sex characteristics of opposite sex [adrogen-secreting tumors or hyperplasia)
• partial (development of one secondary sex characteristic only
  1) premature thelarche (breast budding) - girls 6 months to 2y/o
  2) premature adrenarche (growth of axillary and pubic hair) - 5-8 y/o
  3) can progress to complete d/t estrogen-secreting neoplasms or variatn of normal pubertal development

====
causes
* delayed or incomplete puberty d/t hypergondatropism (inc FSH + LH) and hypogondaotropism (dec LH + FSH)

Question 3

delayed puberty

Answer 3

later than 8-13 age

• most cases here, the HPG or hypothalamic-pituitary-gonadal axis intact but surge of activity stimulates puberty is delayed (GnRH => pituitary => P release LH and FSH; both genders have)
• for males, hormones travel to testes => testosterone
• for females, cause ovaries to produce estrogen

Question 4

Menstrual d/o

Answer 4

• disrupted HPG
• subsequent alteration of hormone production, reception by target organs, or feedback mechanisms

Question 5

Primary dysmenorrhea

Answer 5

• painful menstruation, not associated w/ pelvic disease
• excessive synthesis of prostagladins (or sensitivity to prostagladins) [usually produced when endometrial cells begin to break down during menstruation and release large amounts of inflammatory prostagladins, they cause muscles in your uterus to contract to help expel uteruine lining, higher levels can cause severe menstrual cramps and contractions may constrict blood vessels around uterus]
• l/t myometrium to contract and constrict blood vessels => ischemic pain

Question 6

Secondary amennorhea

Answer 6

• continued absence of menarche for 3 months or 6 months of irregular menses in women who have previously menstrated
• this secondary amenorrhea => associated with anovulation
• caused by pregnancy, lactation, stress, chronic illnes

Question 7

Primary amenorrhea

Answer 7

• continued absence of menarche (1st occurrence of menstruation) and menstrual function by age of 13 w/o devleopment of 2ndary sex characteristics, or by age 15 years if changes have occurred

sx

• Hot flashes.
• Nipples leaking milk.
• Vaginal dryness.
• Headaches.
• Vision changes.
• Acne.
• Excess hair growth on your face and body.

Common causes of primary amenorrhea

• Chromosomal or genetic problems that affect your reproductive system, such as Turner syndrome.
• Hormonal issues stemming from problems with your brain or pituitary gland.
• Structural problem with your organs, such as missing parts of your uterus or vagina or having an underdeveloped reproductive system.

Natural (or normal) reasons to miss your period include:

• Pregnancy (the most common cause of secondary amenorrhea).
• Breastfeeding (or lactation amenorrhea).
• Menopause.
• Having surgery to remove your uterus or ovaries.

Question 8

How is amenorrhea divided into?

Answer 8

compartments that reflect the underlying d/o
1) Compartment I - d/o of outflow tract (expulsion of normal secretions from the cervix and vagina. Outflow is also critical for menstrual efflux) or uterine target organ (FSH + LH => ovaries; GH => all tissue)
2) Compartment II, disorder of the ovary
3) Compartment III, d/o of anterior pituitary
4) Compartment IV; disorder of CNS or hypothalamic factors

Question 9

AUB or abnormal uterine bleeding

Answer 9

• abnormal in duration, volume, frequency, regularity, combination of these factors

Question 10

Polycystic ovary syndrome (PCOS)

Answer 10

• syndrome in which at least 2 of following are present:
  1) irregular ovulation or anovulation
  2) elevated levels of androgen or clinical signs of hyperandrogenism (testosterone)
  3) polycystic ovaries - numerous small cysts and fluid-filled that form inside ovary

prolonged anovulation
* l/t infertility
* menstrual bleeding d/o
* hirsuitism (grwoth of dark + coarse har in male-like pattern d/t androgens
* acne
* endometrial hyperplasia (precancerous condtion in which there is irregular thickening of uterine lining - lining cavity)
* CV disease
* DM in women w/ hyperinsulinemia (high levels of insulin in blood)

sx:

• Missed periods, irregular periods, or very light periods
• Ovaries that are large or have many cysts
• Excess body hair, including the chest, stomach, and back (hirsutism)
• Weight gain, especially around the belly (abdomen)
• Acne or oily skin
• Male-pattern baldness or thinning hair
• Infertility
• Small pieces of excess skin on the neck or armpits (skin tags)
• Dark or thick skin patches on the back of the neck, in the armpits, and under the breasts

Tx:
* birth control pills (control cycles, lower androgen, reduce acne)
* diabetes medication
* change in diet and activity
* meds for hairgrowth or acne

Question 11

PMS (Premenstrual syndrome)

Answer 11

• cyclic recurrence of physical, psychologic, or behavioral changes distressing enough to disrupt activities or interpersonal relationships
• about 300 of these 3 kinds of sx have been attributed to PMS

1) emotional - mainly depression, anger, irritability and fatigue [most distressing]
2) physical - less problematic

Tx is symptomatic and includes self-help techniques, lifestyle changes, conseuling, and SSRIs

Question 12

Infection and inflammation of female genitalia

Answer 12

1) exogenous pathogens (STDs)
2) overproliferation of microorganisms that normally population genital tract

Question 13

Pelvic [triangle] inflammatory disease (PID)

Answer 13

• acute ascending polymicrobial infection of upper genital tract (uterus, fallopian tubes, ovaries, and cervix)
• Caused by sexually transmitted pathogens that are allowed to ascend b/c disruption in vaginal flora

Question 14

Vaginitis

Answer 14

• vaginal infection
• d/t variety of microorganisms, or irritants or disruption in vaginal pH
• induces vaginal irritation, itching, burning, odor, or abnormal dischrage

Primary forms
1) Vulvovaginal candidiasis (vanginal yeast infection); overgrowth of the fungus candida => causig skin around vagina to burn + itch + possibly change vaginal disrcharge (antifungal medication)
* candida resides in your mouth, digestive tract, and vagina while other bacteria help keep its growth under control (when out of balance, it grows rapidly and can get a yeast infection)
* redness to vulva (outside parts of vagina)
* most common during puberty and before menopause
* other factors that increase risk - antibiotics, birth control pill, or certain steroids + pregnancy + immune system suppressed + diabetes + vaginal deodorant or scented tampons

sx

• An itchy or burning sensation in your vagina and vulva.
• A thick, white vaginal discharge with the consistency of cottage cheese.
• Redness and swelling of your vagina and vulva.
• Small cuts or tiny cracks in the skin of your vulva because of fragile skin in the area.
• A burning feeling when you pee.

tx
* fluconazole (oral or topical)
* miconazole or terconazole

==

2) bacterial vaginosis
* most common
* overgrowth of a specific bacteria (usually balance each other out
* fishy odor

sx:
Up to 84% of people with bacterial vaginosis don’t have symptoms. If you do, you may have:

• Off-white, gray or greenish-colored vaginal discharge.
• Fishy-smelling vaginal discharge, especially after sex.
• Vaginal itching or irritation.
• A burning feeling when you pee.

tx
* metronidazole or clindamycin (gel, cream, pills) - both AB

==

3) trichomoniasis – common, but curable, sexually transmitted infection (STI). A parasite causes trich (parasite is called Trichomonas vaginalis) – can come from semen and vaginal fluids. Most people who have trich don’t have symptoms. Treatment for trich involves taking antibiotics.
* highly contagious

• sx occur within 5-28 days after exposure
  include:
• Froth-like discharge from your penis.
• Burning after ejaculation or painful urination.
• Irritation or itching inside your penis.
• Thin (or sometimes foamy) white, yellow or greenish vaginal discharge that has a bad odor.
• Irritation, soreness or redness around the opening of your vagina.
• Pain or discomfort during intercourse or when peeing.

Not caused by UTI

TX
1) metronidazole

Question 15

Cervictis

Answer 15

• inflammation of cervix
• can be acute (mucopurulent cervictis) or chronic

mucopurlent cervictis (chlamydia, gonorrhea, or other germs)

• vaginal discharge​
• bleeding between periods or after sex
• pain in the abdomen
• pain during or after vaginal sex

If MPC isn’t treated, it can spread up into the uterus, fallopian tubes, and ovaries. This can cause a serious infection called pelvic inflammatory disease (PID). PID can cause pain in the lower abdomen, infertility, and increase your risk of tubal pregnancies.

These effects can be prevented if you get early STI testing and treatment.

tx antibiotics

Question 16

Vulvovestibulitis

Answer 16

• inflammation of skin of the vulva
• can be caused by chemical and mechanical irritants, allergens, skin d/o, nerve problems, or vaginal infections (such as candidiasis)

sx
* Pain from pressure (sitting, biking, working out, tight clothes, touch)
* Pain from sex or using a tampon.
* A burning feeling.
* Stinging.
* Feeling raw.
* Peeing a lot, or suddenly feeling like you have to pee.
* An unusual or irritating vaginal discharge.

tx
self care
* Try different detergents.
* Use a mild soap.
* Don’t use scented pads or tampons.
* Don’t wear tight clothes.
* Wear clothes that breathe, such as cotton.
* Avoid activities that may irritate your vulva, like biking.
* Cut back on alcohol, caffeine, and artificial sweeteners.
* Try witch hazel pads or cold compresses.
* Pour lukewarm water over your vulva after you pee.
* Soak in a lukewarm bath with 4-5 tablespoons of baking soda for 10-15 minutes, and do it up to three times a day. But avoid hot tubs and hot baths.
* Use petroleum jelly or vegetable shortening (Crisco) on your skin to keep it moist.

medications - pain, itching, or nerve block mediations
biofeedback + physical therapy
laser tx!

Question 17

Bartholinitis

Answer 17

• bartholin cyst
• inflammation of ducts that lead from bartholin glands (behind vagina, secrete lubcriant for intercourse) to surface of vulva
• inflammation blocks glands => preventing outflow of glandular secretions
• trauma or infection related

Question 18

Pelvic organ prolapse

Answer 18

1) uterine prolapse (uterus descend into vagina, can come out of opening [ages 50-90])
2) cystocele (bladder buldges into vaginal space [d/t tissue between bladder and vaginal wall weakening] => compressed vagina
3) rectocele (rectum falls d/t weak wall between rectum and vaginal wall
4) urtherocele (urethra moves and presses against vagina wall)

• caused by loss of support provided by pelvic muscles and fascia (band of thin, fibrous connective tissue that wraps around and supports every structure in your body.)
• age + pelvic trauma can be factors
• women w/ a familial or genetic predisposition have higher risk
• vaginal childbirths, constipation, obesity, hysterectomy (remove uterus)

Question 19

Benign growths and proliferative condtions of female reproductive tract

Answer 19

• affect ovaries or uterine tissues

1) benign ovarian cysts
* develop from mature ovarian follicles that do no release their ova (follicular cyst) or a corpus luteum persists unnaturally instead of degenerating (corpus albicans is usual product, but in this case its a corpus luteum cyst
* usually regress spontaneously

=== rest are uterine types ===

2) endometrial polpys - overgrowth of endometrial tissue and often cause abnormal

3) Leiomyomas (uterine fibroids) - tumors that come from muscle layer or myometrium of uterus; increases between 30-50; most myomas remain small and asymptomatic

4) Endometriosis - presence of functional endometrial tissue [cells similar to lining of uterus grow outside uterus] (tissue that responds to hormonal stimulation) at sites outside the uterua
* it causes an inflammatory reaction at site of implantation
* causing pain + infertility
* often involves pelvic tissue and envelop ovaries and fallopian tubes + other organs (such as bowel and bladder)

Question 20

Adenomyosis

Answer 20

• condition where endometrial tissue in lining of uterus grow into muscle wall of uterus; enlarging the uterus and can l/t heavy bleeding
• presence of endometrial glands and stroma inside myometrium

Question 21

Most cancers concern which part of female genitalia?

Answer 21

• uterus (mainly cervix) + ovaries
• rarely vagina

Question 22

HPV (human papillomavirus)

Answer 22

• sexually transmitted infection; high risk
• necessary precursor for developing CIN or Cervical intraepithelial neoplasia and cervical cancer
• CIN - premalignant condition of the uterine cervix. The ectocervix (surface of the cervix that is visualized on vaginal speculum examination) is covered in squamous epithelium, and the endocervix, including the cervical canal, is covered with glandular epithelium.

Cofactors
* smoking, immunosuppression, poor nutrition
* HPV vaccination can substantially reduce risk of cervical cancer

Question 23

Cervical cancer

Answer 23

• comes from cervical epithelium
• progressive neoplastic alterations (formation of neoplasms or tumors):
  1) cervical intraepitheal (form surface or lining) neoplasia (cervical dysplasia - abnormal growth on surface of cervix => squamous intraepithelial lesions or atypical glandular/squamous cells)
  2) cervical carinoma in situ (condition in which abnormal cells that look like cancer cells under a microscope are found only in place where they first formed and have not spread to nearby tissue; at some point can become cancerous and spread into nearby normal tissue) [usually in inner tissue layer]
  3) invasive cervical carcinoma (cancer has spread from surface of cervix to tissue deeper in cervix or other parts)

Question 24

Vaginal cancer

Answer 24

• exposure to DES or diethylstibestrol or first synthetic form of estrogen and prior or concurrent cervical cancer
• similar to cervical cancer, vaginal forms come from epithelium and can be identified as:
  1) intraepithelial neoplasia (cervical dysplasia - squamous/glandular on surface)
  2) carcinoma in situ (deep in layer, only microscopic findings, look like abnormal cells that can be come cancerous)
  3) invasive carcinoma (already spreaded)
• most of these conditions are secondary in nature

Question 25

Vulvar cancer (external sex structures)

Answer 25

• HPV infection or squamous dysplasia (vagina or cervix)

sx —
* chronic vulvar irritation
* pruitus
* bloody discharge
* hard/ulcerated area of vulva or large caluifolwer-like lesions

• peak incidence - postmenopausal women, but younger women can be affected

Question 26

Endometrial cancer

Answer 26

• most common of pelvic region
• risk factors: unopposed estrogen exposure, obesity, infertility, failure to ovulate (release of egg),, early menarche, or late menopause, tamoxifen (antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow // blood clot risk in lungs)
• oral contraceptives use protects against endometrial and ovarian cancers + colorectal [except increased risk of breast and cervical cancer]
• peak incidence 58-60 y/o

Question 27

Risk factors for ovarian cancer

Answer 27

• increased number of total lifetime ovulations
• early menarche, late menopause
• nulliparity - woman never given birth to a child or has never carried a pregnancy
• use of fertility drugs

BRCA1 (makes protein that act as a tumor suppressor / invovled in repairing damaged DNA / regulate other genes and important in embryonic development) , BRCA2 (makes tumor suppression protein / repairs DNA / regulate cytokinesis which is step when fluid surrounding nucleus (cytoplasm) divide to form two new cells) , and HPNCC (Hereditary Nonpolyposis Colorectal Cancer, lynch syndrome [no familial connection] // inherited genetic mutations that impair DNA msimatch repair => colon cancer, including endometrial cancer risk) gene abnormaltiies linked with ovarian cancer
* cause more deaths than any other genital cancer

Question 28

Infertility

Answer 28

• inability to conceive fater 1 year of unprotected intercourse, affects 15% of all couples
• women’s fertility decreases w/ age and older women may opt for intervention moreso
• factors that can impair can be from male, female or both
• ovluation disorders and tubal blockages are most common reasons

list of d/o
* Hypothalamic dysfunction, either hypothyroidism or hyperthyroidism
* Polycystic ovary syndrome (PCOS) - irregular periods, a hormonal imbalance causes your ovaries to enlarge and develop small cysts on the outer edges. Beyond having problems with the menstrual cycle, PCOS can also affect fertility, cardiac function and appearance; including increased testosterone (theory - low levels of insulin trigger this)
* Premature ovarian failure
* Too much prolactin, a hormone that, among many other functions, promotes breast milk production

Question 29

Galactorrhea

Answer 29

• inappropriate lactation
• persistent secretion of milky substance by one or both breasts in nonpregnant, nonlactating women
• it can occur in men too
• most common cause: nonpuerperal hyper prolactinemia (a rise in serum prolactin levels not associated w/ pregnancy and childbirth)
• Hyperprolactinemia can be d/t medications, pituitary tumors, hypothyroidism (increased THR from hypothalamus => causes pituitary gland to produce more TSH => lactotroph hyperplasia [pituitary enlargement], chronic stress, persistent and repeated suckling

Question 30

Benign breast disease

Answer 30

• spectrum of noncancerous changes in breast
  Benign lesions classified as

1) nonproliferating breast lesions (differentiate from high risk proliferative versions)
* simple breast cysts
* papillary apocrine change [a condition that involves the cells lining the inside of the breast duct (epithelium)]
* “Usual hyperplasia” means there is excessive growth of benign cells in an area of the breast, but the cells don’t look abnormal. [lining ducts or lobules of breasts in other cases]
* Fibrocystic changes or physiologic nodularity => not clincally definitive
* Sx affect women ages 30-50; cyclic bilateral breast tenderness and transient breast lumps

2) Proliferative breast disease – breats lesions w/o atypia
* proliferation of ductal epithelium and/or stroma (The cells and tissues that support and give structure to organs, glands, or other tissues in the body // around the ducts and lobules)
* Following structural diverse lesions
a) usual ductal hyperplasia (an overgrowth of cells lining the ducts in the breast, but the cells look very close to normal)
b) intraductal papillomas (benign (non-cancerous), wart-like tumors that grow within the milk ducts of the breast. They are made up of gland tissue along with fibrous tissue and blood vessels (called fibrovascular tissue) ==> clear or bloody nipple discharge (or breast lump) + presence of them increases risk
c) sclerosing adenosis (benign (not cancerous) condition in which scar-like fibrous tissue is found in the breast lobules (the glands that make milk). In sclerosing adenosis, the lobules are larger than normal. This may result in a breast lump that may be large enough to feel.)
d) radial scar (A radial scar is a growth that looks like a scar when the tissue is viewed under a microscope. It has a central core containing benign ducts. Growing out of this core are ducts and lobules that show evidence of unusual changes such as cysts and epithelial hyperplasia (overgrowth of their inner lining). Often, more than one radial scar is present. Another term for this condition is complex sclerosing lesions.
e) simple fibroadenoma - solid breast lump

3) Atypical (atypia) hyperplasia - proliferative breast lesions with atypia
* atypical ductal hyperlasia
* atypical lobular hyperplasia

Question 31

Breast cancer

Answer 31

• most common amongst American women
• occur in women 50 y/o and older
• reproductive risk factors: nulliparity and pregnancy-associated breast cancer (during pregnancy and/or postpartum period)
• familial risk factors: inherited gene syndromes (abnromal BRCA1 and BRCA2 – even with strong family hx can make it more likely)
• environmental and lifestyle - hormonal factors and radiation exposure
• Delayed involution (lactating glands return to a morphology near pre-pregnant state) of mammary gland and increased breast density

Lifetime risk is reduced in parous women (having produced offspring) compared to nulliparous women [but pregnancy must start at young age]. Also looking at family hx, lactation postpartum, and overall parity

Question 32

Breast gland involution after pregnancy and lactation

Answer 32

• uses some of the same tissue remodeling pathways activated during wound healing
• presence of macrophages in the voluting mammary gland contributes to carcinogenesis

Volution is shrinking

Question 33

Most breast cancers are…?

Answer 33

• Adenocarcinomas (starts in glandular tissue which lines certain internal organs and release substances in body) - first arising from ductal and lobular epithelium as carcinoma in situ (for e.g pre-cancer that starts in a milk duct and has not grown into the rest of the breast tissue)
• carcinoma in situ @ early stage, noninvasive proliferation of epithelial cells confined to ducts and lobules

Question 34

Is breast cancer a heterogenous disease?

Answer 34

Yes with diverse molecular, biologic, phenotypic, and pathologic changes
* the cancer itself is heterogenous within the same tumor; cellular subpopulations from different sections of thes ame tumor vary in growth rate, immunogenicity, ability to metastasize, and drug response; influenced by surrounding neighborhood
* subclone groups can exhibit cooperative effort to influence cancer progression

Question 35

EMT or epithelial-to-mesnchymal transition

Answer 35

• involved in generation of tissues + organs during embryogenesis
• important for driving tissue plasticity during development
• this process can be hijacked by cancer progresssion
• EMT reprogramming involved in many cancer processes
  1) suppression of cell death and senescence (aging of whole organisms)
  this process itself is reactivated during wound healing

Question 36

Three main prequisites that must be met for metastatic colonization to succeed

Answer 36

1) capacity to seed and maintain a population of tumor-initiating stem cells
2) ability to create adaptive, organ-specific colonization programs
3) development of a supportive microenvironmental niche

Question 37

Ductal carcinoma in situ (DCIS)

Answer 37

• presence of abnormal cells inside a milk duct in breast
• earliest form of breast cancer
• noninvasive, low risk of becoming invasive and spreading out of milk duct
• proliferative lesions limited to ducts and lobules w/o invasion to basement membrane [under endothelium]

Question 37

Ductal carcinoma in situ (DCIS)

Answer 37

• presence of abnormal cells inside a milk duct in breast
• earliest form of breast cancer
• noninvasive, low risk of becoming invasive and spreading out of milk duct
• proliferative lesions limited to ducts and lobules w/o invasion to basement membrane [under endothelium]

Question 38

First clinical manifestation of breast cancer and tx?

Answer 38

• small painless lump in breast
• palpable lymph nodes in axilla, dimpling of skin, nippe and skin retraction (inverted), discharge, ulcerations, reddened skin, bone pain (d/t bony metastases

tx
* surgery, radiation, chemotherapy, hormone therapy, and biologic therapy