Goljan's chapter 22: Female Repro + Breast Disorders Flashcards
Description and treatment of Candida albicans
- Yeasts and pseudohyphae
- part of normal vaginal flora
- Second most common vaginitis in the US
- Risk factors: diabetes, antibiotics, pregnancy, OCPs
- Pruritic vaginitis with a white discharge and fiery red mucosa
- Treatment: single oral dose of fluconazole or itraconazole
Description and treatment of Chlamydia trachomatis
- Third most common STD; often coexists with Neisseria gonorrhoeae (45% of cases)
- Incubation period 7–12 days after exposure
Infections in males: NSU (sterile pyuria), epididymitis, proctitis - Infections in females: urethritis (sterile pyuria), cervicitis, PID, perihepatitis (FHC syndrome—scar tissue between peritoneum and surface of liver from pus from PID), proctitis, Bartholin gland abscess
- Infections in newborns: conjunctivitis (ophthalmia neonatorum), pneumonia
- Nucleic acid amplification test has the highest sensitivity and specificity
- Treatment: azithromycin or doxycycline
Description and treatment of Gardnerella vaginalis
- Gram-negative rod that causes bacterial vaginosis (most common vaginitis)
- Douching alters the microenvironment by decreasing lactobacilli (gram-positive rods that produce lactic acid and the normal vaginal pH of 3.8–4.5); new or multiple sex partners also predisposes to this vaginitis because pH of semen is alkaline (7.2–7.8), which allows the bacteria to proliferate and produce a malodorous vaginal discharge with a vaginal pH >4.5
- Organisms adhere to (they do not invade) squamous cells producing “clue cells”
- Increased incidence of preterm delivery and low-birth-weight newborns
- Treatment: metronidazole; same treatment in pregnancy
Description and treatment of Haemophilus ducreyi
- STD; gram-negative rod that causes chancroid
- Male dominant disease (10 : 1); high incidence of HIV
- Incubation 4–7 days
- Painful genital and perianal ulcers with suppurative inguinal nodes
- Diagnose with Gram stain (“school of fish” appearance) and culture
- Treatment: ceftriaxone or azithromycin
Description and treatment of HSV-2
- STD; virus remains latent in the sensory ganglia
- Characterized by recurrent vesicles that ulcerate; locations—penis, vulva, cervix, perianal area
- Tzanck preparation: scrapings removed from the base of an ulcer show multinucleated squamous cells with eosinophilic intranuclear inclusions
- Pregnancy: if the virus is shedding, the baby is delivered by cesarean section
- Treatment: acyclovir (decreases recurrences)
Description and treatment of HPV
- Second most common overall STD (a few studies still consider it the most common STD)
- types 6 and 11 (90% of cases; low risk types) produce condyloma acuminata (venereal warts); they are fern-like or flat lesions located in the genital area. Approximately 80% of sexually active women will have acquired HPV by age 50 years
- Virus produces koilocytic change in the squamous epithelium, cells have wrinkled pyknotic nuclei surrounded by a clear halo
- Approximately 90% of the warts spontaneously clear within 2 years (most within 8 months); older women more often have persistent disease, because of a decrease in cellular immunity
- HPV vaccine decreases the risk for developing venereal warts
- Treatment: topical podophyllin, sinecatechin (botanical drug) ointment, α-IFN injection, imiquimod cream, laser phototherapy
Description and treatment Klebsiella granulomatis
- STD; gram-negative coccobacillus that causes granuloma inguinale
- Organism is phagocytized by macrophages (Donovan bodies)
- Creeping, raised sore that heals by scarring; no lymphadenopathy
- Treatment: doxycycline
Description and treatment of Neisseria gonorrhoeae
- Fourth most common STD; gram-negative diplococcus that infects glandular or transitional epithelium; symptoms appear 2–7 days after sexual exposure
- Infection sites are similar to C. trachomatis
- Complications: ectopic pregnancy, male sterility, disseminated gonococcemia (C6–C9 deficiency is a risk factor), septic arthritis, FHC syndrome, disseminated gonococcemia (septic arthritis [knee], tenosynovitis [hands, feet], pustules [hands, feet], women > men)
- Nucleic acid amplification test has the highest sensitivity and specificity; other tests: urethral swab in symptomatic males with Gram stain; endocervical swab for culture
- Treatment: ceftriaxone
Description and treatment of Treponema pallidum
- Fifth most common STD; gram-negative spirochete that causes syphilis
- Primary syphilis: solitary painless, indurated chancre; locations—penis, labia, anus, mouth
- Secondary syphilis: maculopapular rash on trunk, palms, soles; generalized lymphadenopathy; condylomata lata, which are flat lesions in the same area as condylomata acuminata; alopecia (hair loss)
- Tertiary syphilis: neurosyphilis, aortitis, gummas
- Nonspecific screening tests: RPR or VDRL; titers decrease after treatment
- Confirmatory treponemal test: FTA-ABS; positive with or without treatment
- Jarisch-Herxheimer reaction: intensification of the rash in secondary syphilis may occur because of proteins released from dead organisms after treatment with penicillin
- Treatment: penicillin
Description and treatment of Trichomonas vaginalis
- Most current studies consider it to be the most common STD; flagellated protozoan with jerky motility in a wet prep of discharge
- Most women are asymptomatic or have a vaginal discharge; men are asymptomatic carriers who serve as a reservoir for infection in women; increased susceptibility for HIV and increased HIV shedding
- Produces vaginitis, cervicitis, and urethritis, PID, preterm delivery, low-birth-weight babies; strawberry-colored cervix and fiery red vaginal mucosa; greenish, frothy discharge
- Diagnosis: nucleic acid amplification test has the highest sensitivity and specificity; other tests: culture, monoclonal fluorescent antibody staining; oral and rectal tests not recommended
- Treatment: metronidazole (both partners)
What organism most commonly causes a Bartholin gland abscess?
Neisseria gonorrhoeae
What is lichen sclerosis?
- Usually occurs in postmenopausal women
- Thinning of the epidermis
- Parchment-like appearance of the skin
- Small risk for developing squamous cell carcinoma (SCC)
What is Lichen simplex chronicus?
- White plaque-like lesion (leukoplakia)
- Due to squamous cell hyperplasia
- Small risk for developing SCC
Papillary hidradenoma
- Benign tumor of the apocrine sweat gland
- Painful nodule on the labia majora
Vulvar intraepithelial neoplasia (VIN)
- Dysplasia ranges from mild to carcinoma in-situ (CIS)
- Strong association with human papillomavirus (HPV) type 16
- Precursor for developing SCC
Vulvar squamous cell carcinoma
- Most common cancer
- Risk factors: HPV type 16, cigarettes, Immunodeficiency
- Metastasize first to the inguinal nodes
Extramammary Paget disease
- Red, crusted vulvar lesion
- Intraepithelial adenocarcinoma
- Tumor derives from primitive epithelial progenitor cells
- Malignant Paget cells contain mucin
- Mucin is periodic acid–Schiff (PAS) positive.
- Spreads along the epithelium, rarely invades dermis
Vulvar malignant melanoma
- Melanoma cells are histologically similar to Paget cells
- Unlike Paget cells, melanoma cells are PAS negative.
Rokitansky-Küster-Hauser (RKH) syndrome
- A condition where the vagina and uterus are underdeveloped or absent
- Ovaries are usually present and functional.
- Most likely results from a combination of genetic and environmental factors
- Some cases appear to have an autosomal dominant inheritance pattern.
- Anatomic cause of primary amenorrhea
Gartner duct cyst
- Remnant of the wolffian (mesonephric) duct
- Presents as a cyst on the lateral wall of the vagina
Rhabdomyoma
- Benign tumor (? hamartoma) of skeletal muscle (vagina)
- Other locations are the tongue and heart (associated with tuberous sclerosis).
Embryonal rhabdomyosarcoma
- Most common sarcoma in girls
- Malignancy of skeletal muscle (rhabdomyoblasts with striations)
- Occurs in girls
Clear cell adenocarcinoma of the vagina
- Occurs in women with intrauterine exposure to diethylstilbestrol (DES)
- DES was used to prevent a threatened abortion
- DES inhibits müllerian differentiation.
- Müllerian structures include fallopian tubes, uterus, cervix, upper one third of vagina
- Vaginal adenosis is precursor lesion for clear cell adenocarcinoma. Benign remnants of müllerian glands, roduces red, superficial ulcerations in the upper portion of the vagina
- The risk for developing the cancer is small (1 : 1000).
- Cancer involves the upper vagina.
Vaginal squamous cell carcinoma
- Primary SCC is associated with HPV type 16.
- Most cancers are an extension of a cervical SCC into the vagina.
- Primary cancers metastasize to the inguinal lymph nodes.
Where does exocervix begin
Cervical os
Epithelium of exocervix
squamous epithelium
Epithelium of endocervix
- glands, normally lined by mucus-secreting columnar cells
- Endocervical epithelium normally migrates down to the exocervix
Lactobacilli
- gram + rod; produce lactic acid; keeps vaginal pH acidic
Transformation zone (TZ)
site where squamous dysplasia/SCC develop
Acute cervicitis
- Acute inflammation is normally present in the TZ.
- Pathologic acute cervicitis; causative agents include: Chlamydia trachomatis, N. gonorrhoeae, Trichomonas vaginalis, Candida, HSV2, HPV
- Symptoms: Vaginal discharge (most common), Pelvic pain, dyspareunia (painful intercourse), Painful on palpation, bleeds easily when obtaining cultures, Cervical os is erythematous and may be covered by an exudate.
- Diagnosis: DNA probe for C. trachomatis and N. gonorrhoeae (>50% of cases of acute cervicitis), Wet mount for T. vaginalis (jerky movements), Pap smear
Treatment: If culture +, treat w/ abx. If -, cryosurgery is an option
Chronic cervicitis
Occurs when acute cervicitis persists
Follicular cervicitis
- Caused by C. trachomatis
- Pronounced lymphoid infiltrate with germinal centers
- C. trachomatis infects metaplastic squamous cells.
- Cells contain vacuoles (phagosomes) with inclusions (reticulate bodies).
- Reticulate bodies divide into elementary bodies, which are infective particles.
- Cervicitis is the primary source for C. trachomatis, N. gonorrhoeae conjunctivitis (ophthalmia neonatorum), and pneumonia in newborns
Cervical pap smear
- Screening test to rule out squamous dysplasia and cancer, evaluate the hormone status of the woman
- Sample sites: Vagina, exocervix, TZ
Interpretation of pap smear
- Superficial squamous cells = adequate estrogen.
- Intermediate squamous cells = adequate progesterone
- Parabasal cells = lack of estrogen and progesterone
- Normal nonpregnant adult woman: 70% superficial squamous cells, 30% intermediate squamous cells
- Pregnant woman: 100% intermediate squamous cells from progesterone effect
- Elderly woman with lack of estrogen and progesterone: Atrophic smear with parabasal cells and inflammation
- Woman with continuous exposure to estrogen without progesterone: 100% superficial squamous cells (Woman may be taking estrogen without progesterone or she has a tumor secretingestrogen)
Cervical (endocervical) polyp
- Nonneoplastic polyp that protrudes from the cervical os
- Arises from the endocervix
- Most common in perimenopausal women and multigravida women
- Most common between 30 and 50 years of age
- Not precancerous
- Causes: Inflammation, trauma, pregnancy have been implicated.
- Presents with postcoital bleeding, vaginal discharge
- Treatment is surgical excision.
Cervical intraepithelial neoplasia (CIN) epidemiology
- Majority of cases are associated with HPV (Types 6 and 11 low risk, 16 and 18 high risk)
- HPV produces koilocytosis in squamous cells (Clear halo containing a wrinkled, pyknotic nucleus)
- Peak incidence is 35 years of age.
- False negative rate for detecting dysplasia on a cervical Pap smear is ~40%.
- Risk factors: Early age of onset of sexual intercourse, Multiple, high-risk partners, High-risk types of HPV in a biopsy, Smoking, oral contraceptive pills (OCPs), immunodeficiency
Cervical intraepithelial neoplasia (CIN) classification
- CIN I: Mild dysplasia involving the lower one third of the epithelium
- CIN II: Moderate dysplasia involving the lower two thirds of the epithelium
- CIN III: Severe dysplasia to CIS involving the full thickness of the epithelium
Cervical intraepithelial neoplasia (CIN) clinical findings, treatment
- not usually visible to the naked eye and requires colposcopy
- Occasionally, flat to warty condyloma acuminata are visible.
- Colposcopy findings, after application of acetic acid include: White areas with punctation, mosaic pattern, or abnormal vascularity
- Tx: Electrocoagulation, cryotherapy, laser ablation, local surgery (conization)
Cervical cancer
Least common gynecologic cancer; cancer with lowest mortality
- Cervical Pap smear most responsible for decreased incidence/ mortality
- abnormal vaginal bleeding MC sign
- spreads down and out
- renal failure common cause of death
Sequence to menarche
breast budding, growth spurt, pubic hair, axillary hair, menarche
Menstrual cycle
proliferative phase, ovulation, secretory phase, menstruation
What happens during the proliferative phase?
- Estrogen-mediated; most variable phase. Estrogen causes gland proliferation, LH release via positive feedback.
- Stimulates FSH.
- LH surge initiates ovulation.
What happens during ovulation/when does it happen?
Day 14-16 of menstrual cycle.
- Increase in body temperature via progesterone.
- Subnuclear vacuoles in endometrial cells are best sign of ovulation
- Mittelschmerz
What happens during the secretory phase?
Progesterone-mediated; least variable phase
- Increased gland tortuosity and secretion
- Edema of stromal cells
Where does fertilization usually occur?
In the ampullary portion of the fallopian tube
How many days does it take for the egg to implant?
5
What is the Arias-Stella phenomenon?
An exaggerated secretory phase that occurs in pregnancy
What causes menses?
drop-off in serum levels of estrogen and progesterone initiate apoptosis in endometrial cells
Why do newborn baby girls commonly have vaginal bleeding?
Mother’s estrogen causes endometrial hyperplasia followed by a sudden drop of maternal hormones with delivery
What are the functions of FSH?
- Prepares the follicle of the month
- Increases aromatase synthesis in the granulosa cells
- Increases the synthesis of LH receptors
What happens to unstimulated follicles?
They are arrested in meiosis I prophase
What are the functions of LH?
- synthesis of testosterone for conversion by aromatase into estradiol in granulosa cells
- stimulates ovulation
- in secretory phase, increases synthesis of 17-hydroxyprogesterone (17-OH-progesterone)
Steps of conversion from testosterone to estradiol
- LH increases the synthesis of 17-ketosteroids (17-KSs) in the theca interna of the developing follicle (17-KSs are dehydroepiandrosterone (DHEA) and androstenedione)
- DHEA is converted to androstenedione.
- Oxidoreductase converts androstenedione to testosterone.
- Testosterone enters granulosa cells in the developing follicle and aromatase converts it to estradiol (called aromatization).
What hormone changes happen during pregnancy?
1) HCG: Synthesized in the syncytiotrophoblast lining the chorionic villus in the placenta
- Acts as an LH analogue by maintaining the corpus luteum of pregnancy.
- Corpus luteum synthesizes progesterone for ~8 to 10 weeks.
2) Corpus luteum involutes after ~8 to 10 weeks.
- Placenta synthesizes progesterone for the remainder of the pregnancy.
- Spontaneous abortion may occur at this time if placental production of progesterone is inadequate.
How do OCP (oral contraceptive pills) work?
They are a mix of estrogen + progestin.
- low estrogen prevents LH surge and ovulation; progestins cause gland atrophy/ inhibit LH
- inhibits Fallopian tube motility
Estradiol
estrogen of nonpregnant woman
Estrone
Weak estrogen produced during menopause, derived from adipose cell aromatization of androstenedione
Estriol
Primary estrogen of pregnancy, derives from fetal adrenal/liver, placenta, and maternal liver
Androstenedione
Equal derivation from ovaries and adrenal cortex
DHEA
Most is synthesized in the adrenal cortex (80%), remainder is synthesized in the ovaries
DHEA-S
Almost exclusively synthesized in the adrenal cortex
Testosterone
Derived from conversion of androstenedione to testosterone
- Testosterone is synthesized in the ovaries and adrenal glands.
- Testosterone is peripherally converted to 5-α-dihydrotestosterone (DHT) by 5-α-reductase, located in the ovaries, adrenal glands, and liver
What is Sex hormone–binding globulin (SHBG) ?
- Binding protein for testosterone and estrogen
- Primarily synthesized in the liver in both sexes
- Estrogen increases synthesis of SHBG in the liver.
- Androgens, obesity, hypothyroidism all decrease the synthesis of SHBG
- SHBG has a greater binding affinity for testosterone than for estrogen.
- Increased SHBG decreases free testosterone (FT) levels.
- Decreased SHBG increases FT levels.
- Common cause of hirsutism in women
Normal changes in pregnancy
- Increase in RBC mass, BIG increase in plasma volume. Causes decrease in Hb due to dilutional effect, increase in GFR, Creatinine clearance due to increase plasma volume.
- Respiratory alkalosis (estrogen/progesterone stimulate respiratory center)
- Increased serum thyroxine (T4) and cortisol (increase in binding proteins NOT free hormones)
Menopause definition
No menses for 1 year after age 40
Average age of menopause
51 years, genetically determined
Menopause symptoms
Hot flashes, night sweats, mood swings
Hormonal changes in menopause
- Testosterone ↑in menopause: ↑libido in some women
- ↑FSH best marker; ↓estradiol, progesterone
Hirsutism definition
excess hair in normal hair-bearing areas
Virilization definition
hirsutism + male secondary sex characteristics
Male secondary sex characteristics
1) Increased muscle mass
(2) Male hair distribution from mons pubis to umbilicus
(3) Acne
(4) Enlarged clitoris (clitoromegaly)
Cause of hirsutism from ovaries
↑testosterone
Cause of hirsutism from adrenals
↑DHEA-S, testosterone
Most common cause of hirsutism/virilization
PCOS
PCOS associated with:
↑incidence insulin-resistance, obesity, acanthosis nigricans
Pathogenesis of PCOS
increased secretion of LH by the anterior pituitary gland relative to secretion of FSH (LH/FSH ratio >3)
- ↑secretion LH → follicular hyperthecosis (hyperplasia ovarian thecal cells) → ↑production testosterone, androstenedione → hyperandrogenicity (e.g., hirsutism)
Clinical effects of PCOS
chronic anovulation (less aromatization of androgens to estrogen), follicular arrest, subcortical cysts - ↑conversion androstenedione to estrone → ↑endometrial hyperplasia/cancer, breast cancer risk
Menorrhagia
loss of blood >80 mL per period
- Regular normal intervals with excessive flow and duration
Dysmenorrhea
painful menses
Primary dysmenorrhea cause
(a) Only occurs in ovulatory cycles
(b) Due to increased prostaglandin F2α (PGF2α)
• Increases uterine contractions
Secondary dysmenorrhea cause
most common cause is endometriosis
Dysfunctional uterine bleeding (DUB)
abnormal uterine bleeding with no anatomic cause. Most common is menorrhagia
Hypomenorrhea
regular normal intervals with decreased amount of bleeding
Metrorrhagia
irregular intervals with excessive flow and duration
Menometrorrhagia
irregular or excessive bleeding during menstruation and between periods
Oligomenorrhea
menses at intervals >35 days
Polymenorrhea
menses at interval
Anovulatory DUB
most common type DUB; excessive estrogen stimulation; extremes of reproductive life (menarche to age 20, perimenopause)
Ovulatory DUB
inadequate luteal phase; irregular shedding of the endometrium
What does inadequate luteal phase in ovulatory DUB cause
inadequate maturation of corpus luteum; delayed secretory phase due to ↓17-OH progesterone synthesis
What does irregular shedding of the endometrium in ovulatory DUB cause
persistent luteal phase with continued secretion progesterone; mixture proliferative/secretory glands
Primary amenorrhea
absence of menses by 16 years of age
Secondary amenorrhea
absence of menses for >6 months in a patient who has had normal menstrual cycles, most common cause is pregnancy
Hypothalamic/pituitary cause of amenorrhea
↓FSH, LH, estrogen. Causes: anorexia nervosa, prolactinoma, hypopituitarism
Ovarian disorder cause of amenorrhea
↑FSH, LH; ↓estrogen. Causes: Turner syndrome, removal of ovaries
End-organ defect cause of amenorrhea
normal FSH, LH, estrogen. Causes: imperforate hymen, Asherman syndrome, Rokitansky-Küster-Hauser (RKH) syndrome
Asherman syndrome
removal of stratum basalis by excessive curettage
Endometritis
uterine infection following delivery
Acute endometritis
uterine infection following delivery or abortion, group B streptococcus is common pathogen. causes fever, uterine pain, discharge
Chronic endometritis
Causes: Retained placenta, Gonorrhea, intrauterine device (Actinomyces infxn)
Key histologic finding is the presence of plasma cells.
