Exam I pathology Flashcards
1
Q
Vulvar: Bartholin’s (greater vestibular) glands are located on either side of the vagina. They function in the production of mucous and lubrication of the vulva and the vagina. They are normally not palpable, except in thin women.
True/False - blockage of the duct leads to the accumulation of lfuid within the gland causing cyst formation
A
True
*can be associated with N. gonorrhea
2
Q
Vulvar: A patient presents with a soft, painless mass adjacent to the vaginal opening.
You suspect
A
Bartholin duct cyst
*ducts open onto the vulvar vestibule at 4 and 8’ o’clock positions on each side of the vaginal orifice
3
Q
Vulvar: A patient presents with complaints of a painful vulvar mass. She states she has difficulty walking and sitting.
Physical exam reveals a swollen, tender, soft or fluctuant mass +/- purulent discharge.
You suspect a Bartholin gland abscess. What is the etiology? How is it treated?
A
-obstruction and infection of the Bartholin duct
MC: E. coli
Tx: incision and drainage; antibiotics for recurrence or severe infection
4
Q
Vulvar: A patient presents with complaints of pruritus in her vulvar region. PE reveals soft, 1mm tan to pinkish cauliflower shaped, fungating, pedunculated, plaque like warts on her vulva.
Histology reveals:
1. HPV-infected squamous cells with hyperchromatic raisin-like nuclei surrounded by a clear space
She admits to having multiple sexual partners. You suspect
A
Condyloma acuminata
- HPV 6, 11
- contact w/ infected skin or mucosa (sexual contact)
- virus invades mucosa via microabrasions
- warts are highly infectious (not required for transmission)
5
Q
Vulvar: The risk of developing Condyloma acuminata increases with increased number of sexual partners. It may be found in a variety of locations, including the vulva, penis and perineum, or cervix, urethra and anal canal.
True/False - There is a vaccine
A
True
*often asymptomatic
6
Q
Vulvar: ______ is a genital ulcer followed by lymph node involvement. It is caused by C. trachomatis (L1, L2, L3 serotypes). It is MC seen in tropical and subtropical areas of the world.
A
Lymphogranuloma venereum
- scarring of lymphatics – lymphedema; rectal strictures
- unlike chlamydia (which inflammation is limited to site of infection)
7
Q
Vulvar: A patient presents with complaints of recurrent, painful vesicles that ulcerate +/- systemic symptoms (mailaise, HA, fever).
You request a Tzanck smear for Dx, which reveals:
1. multi-nucleated squamous cells with intra-nuclear inclusions.
You suspect
A
HSV-2 (HSV-1 inc. prevalent)
- genital herpes MC ulcerative STD in US
- latent in sensory ganglia (recurrences vary in frequency)
8
Q
Vulvar: ______ refers to infection in a patient without pre-existing antibodies to HSV-1 or HSV-2
Initial presentation van vary from subclinical (asymptomatic) to severe w/ genital ulcers and systemic symptoms. Average incubation period is 4 days (range 2-12 days)
A
- Primary infection
9
Q
Vulvar: ______ refers to the acquisition of genital HSV-1 in a patient with pre-existing antibodies to HSV-2 or acquisition of genital HSV-2 in a patient with pre-existing antibodies to HSV-1.
For example, an individual w/ prior orolabial herpes and HSV1 antibody response, who then develops genital Herpes due to HSV-2 exposure
A
Non-primary first episode infection
- fewer lesions
- less systemic symptoms (b/c abs against one HSV type protect against another)
10
Q
Vulvar: _____ refers to reactivation of the genital HSV
A
Recurrent infection
- common, but less severe than primary/non-primary
- mean duration is shorter (10 vs. 19 days)
11
Q
Vulvar: ______ is a sexually transmitted disease caused by T. pallidum, and is associated with contact with the lesion (very infectious). Clinical manifestation depends upon the stage of the disease
A
Syphillis
- T. pallidum initiatie infection wherever inoculation occurs (lips 2ndary to oral contact)
- causes breaks in the skin (ulcer) and inc. risk of other STI’s (HIV)
12
Q
Vulvar: In ______ syphillis, patients present with a painless chancre (lesion) at site of transmission. As this lesion (chancre) develops, organisms drain into regional lymph nodes and disseminate systemically
A
Primary syphillis
*resolves within 3-12 wks (w/ or w/out Tx)
13
Q
Vulvar: Historically, T. pallidum was identified using darkfield microscopy. Currently, serologic testing is used:
- Screening tests
- Confirmatory tests
____ are non-specific, and include RPR (rapid plasma reagin) and VDRL (venereal disease research laboratory). THe both use a non-treponemal antigen (cardiolipin).
A
Screening tests
- low cost, easy
- screen and monitor therapy (titers dec. w/ effective therapy)
14
Q
Vulvar: Historically, T. pallidum was identified using darkfield microscopy. Currently, serologic testing is used:
- Screening tests
- Confirmatory tests
______ is a specific serologic test used to confirm the presence of T. pallidum (syphillis). It uses treponemal antigens that are more specific. It is more expensive and difficult to perform
A
Fluorescent treponemal antibody-absorption test
*positive for life – cannot use to monitor therapy
15
Q
Vulvar: True/False - Immune response during early infection causes resolution of the primary chancre (even in the absence of therapy). However, the patient still needs antibiotic therapy (PCN) to prevent systemic dissemination of the spirochetes and development of secondary/tertiary syphillis.
A
True
PCN=penicillin
16
Q
Vulvar: A patient presents with fever, HA, malaise, and weight loss. He admits to anorexia, and complains of myalgia.
Physical exam reveals a diffuse and symmetric maculopapular rash that involves the entire trunk and extremities, including the palms and soles.
He reports having a chancre ~4-10 weeks ago, but did not receive treatment for his infection.
You suspect
A
Secondary syphillis
- immune response against the organism
- untreated syphillis = systemic, secondary syphillis
Symptoms:
-rash, condyloma lata, alopecia
17
Q
Vulvar: A patient with secondary syphillis presents with distinctive rash that includes the mucosal surfaces. On these mucosal surfaces, you note raised, gray to white lesions (typically in the warm, moist areas).
You suspect
A
condyloma lata
*mouth, perineum
18
Q
Vulvar: A patient presents with fever, HA, malaise, and weight loss. He admits to anorexia, and complains of myalgia.
On PE you note “moth-eaten” alopecia on the scalp, eyebrows and beard. This is another physical finding of -____
A
secondary syphillis
*resolves with treatment
19
Q
Vulvar: Involvement of the CNS (neurosyphilis) can occur early after infection, and may either present asymptomatic infection or meningitis.
A patient presents with abnormal CSF:
- Lymphocytic pleocytosis
- Inc. protein
- Reactive VDRL
He is otherwise asymptomatic. This is
A
Asymptomatic infection
- Dx based on CSF abnormalities
- weeks to months after initial infection
NOTE: Tx to prevent progression to symptomatic
20
Q
Vulvar: A patient presents 1 year following Dx of syphillis. He complaines of HA, N/V and stiff neck. He exhibits confusion.
On PE you note cranial neuropathies (optic, facial, or auditory). you suspect
A
Symptomatic meningitis
21
Q
Vulvar: ______ is manifestation of treponema pallidum years after initial infection in untreated patients. It mostly involves cardiovascular and/or nervous system
A
Tertiary syphilis
*gummas, heart, neurosyphilis
22
Q
Vulvar: A patient presents with brown-red nodules of varying size. These nodules ulcerate, forming well-circumscribed lesions.
You note these are MC located on the skin and in the bone. You suspect tertiary syphillis. What are these manifestations?
A
Syphilitic gummas
- areas of granulomatous inflammation
- healing of ulcers = extensive scarring/disfigurement
23
Q
Vulvar: A patient presents 10-25 years post-Dx of syphillis. He failed to receive treatment during early disease. He presents with progressive dementia that is increasing in severity. Patient exhibits forgetfulness, and personality changes.
CSF studies reveal:
- Inc. WBC (lymphocytes), protein
- Reactive syphillis (VDRL) on CSF
Imaging reveals atrophy
You suspect
A
Neurosyphillis
- late involvement of brain = progressive dementia
- tabes dorsalis, gummas, cardiomyopathy
24
Q
Vulvar: Tertiary syphillis presents with
- Tabes dorsalis
- Sensory ataxia
- Argyll-Robertson pupil
______ is a disease of the posterior columns and dorsal roots of the spinal cord. It has a long latent period (~20 years), and is relatively uncommon w/ antibiotics.
A
Tabes dorsalis
25
Vulvar: Tertiary syphillis presents with
1. Tabes dorsalis
2. Sensory ataxia
3. Argyll-Robertson pupil
____ is absence of lower extremity reflexes, and impaired proprioception and vibratory sensation
Sensory ataxia
26
Vulvar: Vulvar: Tertiary syphillis presents with
1. Tabes dorsalis
2. Sensory ataxia
3. Argyll-Robertson pupil
___ is small pupil that contracts normally to accommodation, but does not react to light
Argyll-Robertson pupil
27
Vulvar: Tertiary syphillis involves the ______ aorta, resulting in a dilated aorta and aortic regurgitation.
It is most likely secondary to vasculitis (narrowing) of the vasa vasorum (ischemia of the medial wall of the aorta).
Findings include:
1. Plasma cells in infiltrate (endarteritis obliterans)
2. "Tree barking"
ascending aorta
* 15-30 yrs. after
* syphillitic aneurysms can rarely cause dissection
28
Vulvar: A patient presents with:
1. Notched central incisors
2. Mulberry molars
3. Interstitial keratitis w/ blindness
4. Deafness due to 8th CN injury
5. Destruction of nasal septum, soft palate
You suspect
COngenital syphillis
* transplacental infection (after 20 weeks);
* MC w/ primary or secondary (plenty of bacteria)
Hutchinson triad:
--notched central incisors, keratitis, deafness
29
Vulvar: ______ is an acute, self-limited febrile reaction with HA, myalgia, rigors (fever and chills). It is due to release of various mediators from killed organisms (associated with treatment of T. pallidum).
Jarisch-Herxheimer rxn
* can't prevent
* inform patients
* resolve within 12-24 hrs.
30
Vulvar: A patient presents with a painful genital ulcer and inguinal lymphadenopathy.
Gram stain reveals a gram negative rod. You suspect
Chancroid
* Haemophilus ducretyi (STD)
* uncommon in U.S.
31
Vulvar: A pre-menopausal female presents with a dermatologic condition characterized by inflammation, epithelial thinning (white parchment-like, atrophic hypopigmented area), pruritus and pain.
You suspect
Lichen sclerosus
* pre-pubertal and/or postmenopausal
* unknown etiology (maybe genetic; hormonal dec. E2)
* adult onset inc. risk vulvar SCC
* *HLA-DQ7 (T-cell mediated)
32
Vulvar: A patient presents with complaints of pruritus (itching) of her skin. She states she repeatedly rubs and scratches the affected sites.
You note red to brown skin colored plaques on her vulva. You suspect
Lichen simplex chronicus
*thickened epidermis due to rubbing
33
Vulvar: _____ is a pre-malignant lesion of the vulva caused by HPV infection. Patients with these lesions are at increased risk of developing squamous cell carcinoma.
Histology reveals:
1. nuclear irregularity w/ nucleoli and numerous mitotic figures
Vulvar intraepithelial neoplasia
```
*VIN 1: mild = atypia of bottom 1/3
VIN II (moderate) = bottom 2/3
VIN III (severe) = full thickness atypia
```
34
Vulvar: A 67 year old female presents with a plaque, ulcer, or mass (fleshy, nodular, or warty) on the labia majora.
This best describes
Vulvar cancer
* 4th MC gynecologic cancer (after endometrial, ovarian, cervical)
* Dx post-menopause
* may involve labia minora, perineum, clit, mons
35
Vulvar: Many vulvar malignancies are asymptomatic. However, pruritus is common (non-specific). Patients may have bleeding, discharge, and/or enlarge lymph nodes in the groin. THis is less common, but if present may suggest advanced disease.
List the common histologic malignancies
1. Squamous cell MC
2. Melanoma
3. Basal cell carcinoma
4. Adenocarcionma of Bartholin
4. Extramammary Paget's
36
Vulvar: Vulvar cancers tend to spread first to the groin (inguinal-femoral) lymph nodes. Squamous cell carcinoma is the MC histologic type of vulvar cancer.
HPV (16, 18, 33) is the major risk factor for developing squamous cell carcinoma. What are risk factors for HPV infection?
a. early age at first intercourse
b. multiple sexual partners
c. HIV infection
d. cigarette smoking
all of the above
*vulvar dystrophies (lichen sclerosus) 2nd major risk factor for SCC of the vulva
37
Vulvar: A post-menopausal, caucasian female presents to the clinic with vulvar malignancy.
Histology reveals:
1. PAS negative vulvar malignancy
You suspect
Melanoma
| non-pigmented look similar to Paget's, but are PAS -
38
Vulvar: A post-menopausal female presents with a gradually enlarging Bartholin gland. She is otherwise asymptomatic. You suspect?
adenocarcinoma of Bartholin gland
* rare
* DD= Bartholin cysts: MC pre-menopausal
39
Vulvar: A post-menopausal, caucasian female presents to the clinic complaining of pruritis.
On pelvic exam, you note multifocal, eczematoid appearance with well-demarcated, slightly raised edges and a red background.
Histology reveals:
1. Intra-epithelial proliferation of malignant glandula cells (adenocarcinoma)
2. cells are larger than surrounding keratinocytes, and present as small clusters
You suspect
a. Paget's
b. Krukenberg tumor
c. Leiomyoma
d. Rhabodmyoma
Extramammary Paget's disease
* may occur anywhere on vulva, mons, perineum, perianal, inner thigh
* NOT associated with underlying malignancy (unlike disease of nipple)
Dx: based on presence of Mucin (PAS +)
40
Vagina/Cervix: Lactobacilli are normal components of the vaginal flora. They produce acid (from glycogen within the vaginal cells) to maintain the vagina at >4.5 pH. They also play a role in suppression of growth of other organisms.
True/False - suppression of lactoacilli (antibiotics) leads to overgrowth of other bacteria
True
*alter vaginal env = overgrowth of other organisms
41
Vagina: A patient presents with complaints of "fishy" smelling vaginal discharge post-coitus.
Wet prep reveals:
1. Clue cells (gram negative rods attached to sq. epithelial cells)
A whiff test is performed (fishy smell produced w/ addition of 10% KOH) to vaginal secretions. You suspect
Bacterial vaginosis
* overgrowth of gardnerella vaginallis
* smell after sex b/c seminal fluid is alkaline
Tx: Only treat patient (not STD)
42
Vagina: A patient presents with complaints of profuse, forthy, green vaginal discharge.
On pelvic exam you note a fiery red cervix/vagina.
Wet prep reveals: Oval to pear shaped unicellular, flagellated protozoa with jerky motility
You suspect
Trichomonas vaginalis
*STI - treat both partners
43
Vagina: A patient presents with pruritus, burning, and irritation.
On pelvic exam you note fiery red vaginal mucosa with white, curd-like discharge.
Lab reveals budding yeast with pseudohyphae.
You suspect
Candida
*normal part of flora
RF's:
-DM, antibiotics, inc. estrogen (pregnancy, OCP's), immunosuppression (steroids, HIV), heat, moisture, occlusive clothing
44
Vagina: A patient presents with dyspareunia (pain with sex) and vaginal pain (may be asymptomatic).
You note a palpable, tense cyst within the lateral vaginal wall on exam.
Yoususpect
Gartner duct cyst
* uncommon, benign
* within lateral vaginal wall
* develop from remnants of the mesonephric ducts
45
Vagina: DES was a nonsteroidal estrogen used to suppress post-partum lactation and to treat post-menopausal symptoms. It was later used to prevent miscarriages, premature birth and other pregnancy problems. However, it readily crosses the placenta.
True/False - Exposure to DES in utero can lead to development of various abnormalities because it prevents resorption of the vaginal glands in the vaginal mucosa (vaginal adenosis).
True
46
Vagina: A patient presents with complaints of vaginal irritation and post-coital bleeding.
Pelvic exam reveals punctate, red, granular areas of the vagina.
Histology reveals areas of columnar epithelium within squamous epithelium of the vagina/cervical mucosa.
You suspect
Vaginal adenosis
* exposure to DES in utero
* persistence of Mullerian glandular epithelium within the vagina (after birth). It is attributed to failure of the squamous epithelium to completely replace the columnar epithelium
47
Vagina: Young female offspring of women who had received DES during pregnancy are at an increased risk of
clear cell adenocarcinoma
MC 19 y/o
48
Vagina: A 4 year old female presents with a malignant tumor of SK muscle.
PE reveals grape-like clusters. protruding from the vagina
Histology reveals striated, rhabdomyoblasts.
You suspect
Embryonal rhabdomyosarcoma
*sarcoma botryoides
49
Vagina: _____ Is a primary tumor of the vagina, and is rare. It is usually secondary to extension of swuamous cell carcinoma of the cervix.
It is commonly associated with HPV. It arises from vaginal intra-epithelail neoplasia.
Squamous cell carcinoma
* metastatic spread:
- -upper 1/3 of vagina to iliac nodes
- -lower 2/3 of vagina to inguinal nodes
50
Cervix: The cervix is composed of three types of histology:
1. Ectocervix (strat. squamous)
2. Endocervix (columnar mucous)
3. Junction b/t the two (squamocolumnar/transformation zone)
The ______ is the area where the two epithelium meet. Chronic irritation in this region leads to the development of squamous metaplasia. This is important because these cells are susceptible to HPV infection, and serves as a site of cervical dysplasia/cancer formation.
transformation zone
51
Cervix: A patient presents with mucopurulent exudate in the endocervical canal (or swab). Her endocervix appears "friable" with easy bleeding induced when the swab is passed through the os.
You suspect
Cervicitis
*inflammation of cervix
52
Cervix: Chlamydia trachomatis (serotypes D-K) is an STD that causes mucosal infections of the genital tract (cervix, tubes, endometrium, urethra and epididymus). Incubation is 7-12 days.
How is diagnosed? How do you Tx?
Dx: DNA probe of vaginal swab
Tx: both patient and sex partner; doxycycline
NOTE: serotypes A, B, C = trachoma (conjuntivitis - blindness; endemic in Africa)
53
Cervix: Opthalmia neonatorum (neonatal conjuntivitis) can arise secondary to passage through the infected birth canal.
In N. gonorrhea, it causes a _____ conjuntivitis seen in the 1st week of life. In chlamydia trachomatis, it causes an initial _____, then becomes mucupurulent.
1. N. gonorrhea: mucopurulent
2. Chlamydia: watery, then mucopurulent
- -2nd week
54
Cervix: Chlamydia trachomatis are obligate intracellular bacteria that infect metaplastic squamous cells in the endocervix. These cells were previously endocervical glandular cells that underwent squamous metaplasia due to irritation from acid pH in the vagina.
What is the infectious form of chlamydia trachomatis?
Elementary body
1. taken up by host cell (receptor-mediated endo)
2. inside endosome - becomes active reticulate body
3. reticulate body replicates = new EB's that infect new cells
55
Cervix: _____ is an STI with an incubation of 2-7 days. Manifestations range from asymptomatic to disseminated infection (women during menses, lacking terminal complement C5-C9).
It commonly presents with urethritis in men, and cervicitis in women.
N. gonorrhea
*cervicitis may lead to PID and infertility
Dx: DNA probe
56
Cervix: A patient presents with fever (102F), chills, and a papular rash on her trunk and distal extremities. She complains of joint pain (arthritis) and tenosynovitis (knees, hands/wrists, feet/ankles).
Gram stain reveals gram (-) diploccocus.
You suspect disseminated gonococcal infection. What are the causes?
1. Menses
2. Terminal complment deficiency
* skin/joint = immune complex deposition
* true septic arthritis can occur
57
Cervix: A 21 year old female presents with complaints of severe acute lower abdominal pain.
You note vaginal discharge on pelvic exam, and cervical motion tenderness (Chandelier sign) during the exam.
Gross reveals:
1. Inflammatory mass involving adnexa ("tubo-ovarian abscess")
She has a history of multiple sex partners, and admits to having a previous STD 3 months ago. You suspect
Pelvic inflammatory disease
- C. trachomatis predominant
- often polymicrobial with N. gonorrhea and Gardnerella
DD: appendicitis, cervicitis, UTI, endometriosis, ectopic pregnancy (mandatory in workup of childbearing age w/ abdominal pain)
58
Cervix: Pelvic inflammatory disease involves the endometrium (endometritis), fallopian tubes (salpingitis) and ovaries (oophoritis) by ascending cerval infection.
True/False - Involvement of the fallopian tube can lead to scarring and increases risk of infertility and ectopic pregnancy.
True
* other complications:
- -Fitz-Hugh Curtis: violin string adhesions (secondary to infection/inflamed perihepatic structures)
59
Cervix: HPV is a DNA virus that is typed according to its DNA sequence. It has high and low risk types based on its ability to cause cervical cancer.
WHat are the high risk? low risk?
HIgh risk: HPV-16 (MC), 18
Low risk: 6, 11
--vulvar, perineal, perianal warts (condylomata acuminata)
60
Cervix: Genital HPV infections are extremely common, with prevalence peaking during ages 20-24. This is related to the onset of sexual activity. Prevalence decreases due to acquisition of immunity and inc. of monogaminity w/ age.
Treu/False - Most infections are transient, and eliminated by the immune system. Duration of infection is often related to HPV type with higher risk strains lasting longer.
True
*persistent infection inc. risk of cervical dysplasia, subsequent carcinoma
61
Cervix: HPV infects metaplastic squamous cells at the squamocolumnar junction (transformation zone). This can lead to development of cervical dysplasia and cancer.
True/False - Although many women are infected with HPV, few develop cancer. This suggests that other factors play a role in determining regression or persistence of the infection and cancer development.
True
*factors: smoking, host immune status
62
Cervix: HPV viral proteins interfere with tumor suppressor enabling continued cell proliferation, and acquisition of additional mutations that can lead to cancer.
What are the proteins involved?
1. E6 - binds p53, telomerase (inc. expression)
| 2. HPV E7 - binds RB (inhibits p21)
63
Cervix: Cervical dysplasia occurs in different grades:
1. Mild dysplasia (CIN I) - low grade SIL
2. Moderate dysplasia (CIN II) - high grade SIL
3. Severe dysplasia (CIN III) - high grade SIL
4. Carcinoma in situ (CIN III) - high grade SIL
_____ is not treated as a pre-malignant lesion because it does not progress directly into invasive carcinoma. Most cases regress spontaneously, with only a small % progressing to HSIL.
LSIL
*atypical squamous cells confined to the lower 1/3 of the epithelium
64
Cervix: Cervical dysplasia occurs in different grades:
1. Mild dysplasia (CIN I) - low grade SIL
2. Moderate dysplasia (CIN II) - high grade SIL
3. Severe dysplasia (CIN III) - high grade SIL
4. Carcinoma in situ (CIN III) - high grade SIL
____ is due to progressive disruption of the cell cycle, leading to inc. cell proliferation, and dec./arrested epithelial maturation. It may become irreversible leading to malignancy.
HSIL
* higher risk of cancer
* extend higher than the lower 1/3
65
Cerix: True/False - Cervical dysplasia is diagnosed based on presence/ID of nuclear atypia (nuclear enlargement, hyperchromasia, and variation in nuclear size and shape).
It is associated with viral cytopathic effect (koilocytes), or nuclear alterations associated with a perinuclear halo
True
66
Cervix: Most LSIL and ALL of HSIL are associated with high risk HPV's (16 MC). The majority of HSIL's develop from LSIL's, however, some develop de novo.
True/False - It is difficult to predict the outcome in an individual patient, however, progression to invasive carcinoma, when it occurs, takes place over a period of years.
True
LSIL: 60% regress; 30% persist; 10% to HSIL
HSIL: 30% regress; 60% persist; 10% to carcinoma
67
Cervix: The mean age of a patient with invasive cervical carcinoma is 45.
What is the MC histologic subtype?
Squamous cell carcinoma
2nd MC: adenocarcinoma
68
Cervix: Cervical cancer usually occurs in women who do not have routine pap smears.
1. Treatment of microinvasive carcinoma involves _____, 2. Treatment of invasive tumors involves ______.
1. Microinvasive: cervical cone excision
2. Invasive: hysterectomy w/ lymph node dissection +/- radiation and chemo
Prognosis:
- -based on stage at Dx
- -5 year survival 100% in microinvasive
- -< 50% survival if extend beyond pelvis
69
Cervix: True/False - Patients with advanced cervical cancer often die due to local tumor extension (e.g. ureteral obstruction, pyelonephritis, and uremia) rather than from distant metastases
True
70
Cervix: A patient presents with a benign, exophytic outgrowth arising within the endocervical canal.
She admits to vaginal spotting.
You reassure her it can be cured by excision, because it is_____
Endocervical polyp
71
Uterus: Paramesonephric ducts fuse along the midline to form the upper 2/3 of the vagina, the cervix, uterus and fallopian tubes.
The cranial end of the fused ducts form the _____, while the caudal end form the _______. Lower segments fuse between 7th-9th wks gestation.
1. uterus
2. upper 2/3 vagina
*midline septum present in uterine cavity -- regresses at 20 weeks (abnormal if persists)
72
Uterus: A patient presents with primary amenorrhea (anatomic issue).
Female exam reveals normal female external genitalia, normal breast development, and presence of functional ovaries. However, you note absence of the vagina and variation in uterine development. You suspect
Mayer Rokitansky-Kuster Hauser syndrome
* due to Mullerian agenesis
* renal anomalies common
* hypoplastic uterus, absent cervix and vaginal atresia, but normal ovaries
73
Uterus: _____ is a uterus formed from only 1 of the paired Mullerian ducts, while the other duct does not develop, or is rudimentary
unicornate
*unicorn = 1 horn = 1 mullerian duct
74
Uterus: _____ uterus in which the fundus is indented (>1cm). The vagina is generally normal. It is due to partial fusion of the mullerian ducts
Bicornate uterus
75
Uterus: ______ occurs when the two mullerian ducts fail to fuse. Duplication is limited to the uterus and cervix
Uterine didelphys (double uterus)
76
Uterus: A patient presents who is genetically male, but is resistant to male hormones. Genetically, he is 46 XY, but lacks functional androgen receptors.
Patient presents with normal female external genitalia, including the distal vagina, normal testes (in inguinal canal), but absent internal genitalia. Breast development is noted. You suspect
Androgen insensitivity syndrome
*lack internal genitalia (Sertoli produce MIF - involution of mullerian system)
* normal breast (testosterone converted to estrogen)
* normal testosterone from Leydig - normal testes
77
Uterus: A patient presents with short stature, sausage-like fingers and toes, and a webbed neck.
She exhibits a flat, broad (shield shaped) chest with widely spaced nipples. Low hairline is present as well as cubitus valgus (wide carrying angle of elbow).
Pelvic exam reveals rudimentary "streak" ovaries with little E2 production (primary hypogonadism).
Breast exam reveals limited breast development.
You suspect
Turner syndrome (45, X)
* inc. FSH/LH = hypergonadotropic hypogonadism
* inc. risk coarctation of aorta
78
Uterus: _____ is characterized by scarring within the uterine cavity. It is typically secondary to intrauterine trauma associated with a surgical procedure.
If symptoms are present (i.e. infertility or amenorrhea) it is known as "Asherman syndrome"
Intrauterine adhesions
* Severity varies:
1. mild: thin bands tissue b/t surfaces
2. severe complete obliteration of the cavity
79
Uterus: A patient presents with fever and complaints of uterine tenderness with abdominal pain.
On pelvic exam, you note foul vaginal discharge.
Histology reveals:
1. Plasma cells within endometrial stroma
You suspect
a. endometritis
b. bacterial vaginosis
c. chlamydia infection
d. serous cell tumor
Endometritis
due to: post-partum complication (retained products of conception - Group B strep; IUD - actinomyces)
80
Uterus: A patient presents with abnormal bleeding.
Pelvic exam reveals hyperplastic overgrowths of endometrial tissue (glands and stroma) WITHIN the endometrial wall. These growths form exophytic masses that project above the surface of the endometrium.
You suspect
Endometrial polyps
* benign, but may result in hperplasia or adenocarcinoma
* express E2 and P receptors
* tamoxifen inc. risk due to E2-like effect
81
Uterus: A patient presents with complaints of pain during menses (dysmenorrhea) and dyspareunia.
Pelvic exam reveals endometrial glands/stroma WITHIN the myometrium and a globular, uniformly enlarged uterus.
Adenomyosis
* hemorrhage during menses causes pain
* maybe due to invagination of stratum basalis into myometrium
82
Uterus: ______ is characterized by presence of endometrial glands and stroma OUTSIDE the uterine lining.
Theories of pathogenesis include:
1. retrograde flow of menstrual endometrium through fallopian tubes (MC)
2. spread through blood vessels and lymph
3. metaplastic theory (endometrial differentiation of coelomic epithelium)
Endometriosis
*commonly in ovaries, fallopian tubes, elsewhere in pelvis, large/small intestine, appendiz, abdominal wall (C-section scars)
83
Uterus: Which of the following is a potential complication of endometriosis?
a. infertility
b. pain with menses (dysmenorrhea)
c. painful intercourse (dypareunia)
d. bowel obstruction/bleeding
all of the above
*painful BM's during menses (bleeding implants on rectum are stretched)
84
Uterus: Endometrial hyperplasia is overgrowth of the endometrial glands (realtive to the stroma) resulting in an increased gland to stroma ratio.
It is due to excess ____ stimulation of the endometrium, and is associated with:
1. Obesity (inc. aromatase activity)
2. Polycystic ovarian syndrome
3. Functioning granulosa tumors of the ovary
4. Unopposed estrogen therapy (HRT)
E2 (estrogen)
* simple vs. complex (degree of architectural crowding)
* with or without atypia (cytologic atypia of nuclei)
85
Uterus: True/False - There is inc. risk of endometrial carcinoma with inc. degrees of architectural crowding and with the presence of nuclear atypia
True
1. without atypia
- -progression to cancer is unusual
- -Tx medially
2. with atypia
- -high risk progression (may already have cancer, not found)
- -Tx: hysterectomy
86
Uterus: _____ is the MC invasive cancer of the female genital tract. It is similar to other cancers in that development of carcinoma is stepwise, with genetic alterations in tumor suppressor and oncogenes (PTEN -- MLH-1 -- KRAS)
Endometrial carcinoma
87
Uterus: ___ acts as a tumor suppressor gene through action of its phosphatase protein product.
It blocks PI3K/AKT signalling pathway, regulating cell division and preventing uncontrolled cell growth. Mutation is implicated in endometrial carcinoma
PTEN
88
Uterus: A 55 year old female presents with post-menopausal bleeding.
Gross reveals: Fungating mass.
Histology reveals: endometroid adenocarcinoma.
You suspect endometrial carcinoma. How do you diagnose?
a. Histologic (e.g. currettage/biopsy)
b. Serum levels
c. PTEN
d. Clinical Dx only
Histologic (currettage/biopsy)
*no screening tool
**MC due to long term exposure to estrogen (nulliparous, early menarche, late menopause, PCOS, obesity)
89
Uterus: Endometrial carcinoma initially invades the myometrium, followed by direct extesnion to adjacent structures/organs.
True/False - It can metastasize by lymphatic spread to regional lymph nodes or undergo hematogenous spread to lungs, liver and bones.
True
90
Uterus: A patient presents to the clinic with complaints of bleeding and inc. urinary frequency (compression of bladder). She reports a history of impaired fertility.
Pelvic exam reveals a benign SM tumor within the myometrium.
Histology reveals tan, non-hemorrhagic leiomyomata.
You suspect
Leiomyoma
*clinical symptoms due to mechanical effects
91
Uterus: ______ is a rare, malignant SM tumor that most often arises de novo (not from pre-existing leiomyoma). It is most often seen in 40-60y/o and may metastasize hemtaogenously to the lungs, bone and brain.
Histology reveals inc. cellularity, hyperchromasia and mitotic activity
a. Leiomyosarcoma
b. Adenoma
c. ovarian cyst
d. yolk sac tumor
Leiomyosarcoma
*often recurrent
92
Ovaries: ____ is a non-neoplastic ovarian mass (MC type). It occurs from accumulation of fluid within the ovarian follicle.
It may rupture, producing sterile peritonitis with pain.
a. follicular cyst
b. ovarian tumor
c. yolk sac tumor
d. adenoma
Follicular cyst
*spontaneous regression
93
Ovaries: LH stimulates the ____ cell to produce androgens (testosterone and androstenedione).
Aromatase enzyme converts excess androgens to estrogens. Insulin stimulates this process as well.
theca cells
94
Ovaries: A patient presents with infertility and amenorrhea (anovulation). You note acne and hirsutism.
Ultrasound reveals polycystic ovaries.
You suspect polycystic ovarian syndrome. What is the pathogenesis of PCOS?
Inc. LH:FSH (>3:1)
* LH -- hyperplasia of ovarian theca cells and inc. androgens
* dec. FSH (to LH) -- follicular "arrest" (don't mature) and formation of subcortical cysts
95
Ovaries: In PCOS, aromatization of androgens to estrone can increase the risk of endometrial hyperplasia and carcinoma.
True/False - Hyperinsulinism (obesity and type 2 DM) can also contribute to PCOS because insulin stimulates androgen production
True
96
Ovaries: A 70 year old female presents with complaints of vaginal bleeding, bloating and constipation. She reports 10 lb. weight loss and early satiety. She admits to reflux after eating and feeling pressure on her bladder.
You note shortness of breath during your physical exam.
Histology reveals tumor lined by ciliated cells (tubal like epithelium) + psamoma bodies.
You suspect
Serous Ovarian tumor (surface derived)
*most malignant ovarian tumors have spread by the time of Dx = poor prognosis
**may be bilateral
97
Ovaries: Most ovarian tumors are benign (ages 20-45) and inc. risk of malignancy with inc. age (45-65). Which of the following is also a risk factor for ovarian malignancy?
a. inc. age
b. nulliparity
c. BRCA-1
d. Turner syndrome
all of the above
* malignant usually > 45 years
* nulliparous: inc. ovulatory cycles = inc. risk surface derived tumors (MC)
* genetic
98
Ovaries: Genetic risk factors of ovarian tumors include
1. BRCA-1 and BRCA-2
2. Lynch Syndrome
3. Turner syndrome
4. Peutz-Jegher syndrome
____ are genes that produce tumor suppressor proteins. Estimated risk of ovarian cancer is 20-60% by age 70. Most often produce high grade serous tumors, and breast cancer.
BRCAs
99
Ovaries: Genetic risk factors of ovarian tumors include
1. BRCA-1 and BRCA-2
2. Lynch Syndrome
3. Turner syndrome
4. Peutz-Jegher syndrome
______ is due to mutations in mismatch repair and leads to inc. risk colon, endometrial, ovraian and stomach cancers
Lynch syndrome
*hereditary non-polyposis (HNPCC)
100
Ovaries: Genetic risk factors of ovarian tumors include
1. BRCA-1 and BRCA-2
2. Lynch Syndrome
3. Turner syndrome
4. Peutz-Jegher syndrome
___ leads to inc. risk of dysgerminoma
Turner, 45 X
101
Ovaries: Genetic risk factors of ovarian tumors include
1. BRCA-1 and BRCA-2
2. Lynch Syndrome
3. Turner syndrome
4. Peutz-Jegher syndrome
____ is characterized by mucocutaneous pigmented lesions, hamartomatous polyps in the GI tract, and inc. risk malignancy of the ovaries, etc.
Peutz-Jegher
102
Ovaries: ______ are surface derived ovarian tumors that are lined by columnar mucous secreting cells.
1. _____ is benign
2. ____ is malignant
Seeding may produce pseudomyxoma peritonei
1. mucinous cystadenoma
| 2. muciinous cystadenocarcinoma
103
Ovaries: _____ is a benign, surface-derived ovarian tumor characterized by transitional type epithelium (like in the bladder) and "coffee bean" nuclei
Brenner tumor
104
Ovaries: A patient presents with a benign ovarian germ cell tumor. Her tumor contains tissue from each of the germ cell layers, including: hair, teeth, cartilage, thyroid, skin, GI tract and muscle.
You suspect
Teratoma
* MC germ cell tumor
* association w/ NMDA receptor encephalitis
105
Ovaries: An adolescent patient (or young adult) presents with an ovarian (germ cell) tumor. She complains of rapid growth with abdominal enlargement and pain.
Histology reveals:
1. Sheets of uniform cells w/ clear glycogen filled cytoplasm and central nuclei
2. Fibrous septa w/ lymphocytes traversing tumor
You suspect
a. dysgerminoma
b. yolk sac tumor
c. cervical dysplasia
d. cervical adenoma
Dysgerminoma
* analogous to seminoma in male (but more rare)
* Inc. LDH, Inc. hcG
* Turner's syndrome*
106
Ovaries: A young female presents with complaints of abdominal pain and a noticeable pelvic mass.
Histology reveals:
1. Schiller-Duval bodies (fibrovascular papillary structure + central vessels) lined by malignant cuboidal cells
2. Pink hyaline globules
Labs reveal:
1. Inc. serum AFP
You suspect
Yolk sac tumor (germ cell tumor)
*AFP = monitor Tx response and post-Tx surveillance
107
Ovaries: A patient presents with a rare, highly malignant tumor comprise of syncitiotrophoblasts and cytotrophoblasts.
Labs reveal elevated serum hcG levels.
You suspect early hematogenous metastasis (lung, liver and brain) based on the type of tumor. WHat tumor do you suspect?
Choriocarcinoma
*serum hcG = monitor Tx response
108
Ovarian sex cord stromal tumors: _____ is a stromal tumor that secretes estrogen. It can cause precocious puberty in kids, and endometrial hyperplasia/cancer in adults.
Histology reveals: Call-Exner bodies
Granulosa cell tumor
109
Ovarian sex cord stromal tumor:
1. ____ secretes androgens. It is distinguished by Reinke crystals.
2. ____ is associated with Meig's syndrome (ovarian fibroma, pleural effusion, ascites). Histology reveals bundles of spindled fibroblasts
1. Sertoli-Leydig tumor
2. Fibroma
- -resolves w/ tumor removal
110
Metastatic tumors: Metastases to the ovaries are common (MC endometrium, breast, colon, stomach, cervix).
_____ is a metastatic tumor with signaet ring cells (from primary gastric carcinoma).
Krukenberg tumor
*PAS + (mucin)
111
Metastatic tumors: ______ are associated with mucinous tumors (ovarian and appendiceal).
Histology reveals large pools of mucin. Gross shows a tumor w/ gelatinous material (mucin).
Pseudomyxoma peritonei (mucinous ascites)
112
Ovaries: True/False - Peithelial tumors tend to be bilateral, benign tumors that can be resected and cured. However, most ovarian carcinoma present with high stage disease with mild symptoms until enlarged. The MC symptoms includepelvic pressure, lower abdominal pain, abdominal enlargement, dysuria and vaginal bleeding
True
**CA-125 used to monitor recurrence/progression
113
Micro pharm: What is the treatment for T. pallidum?
1. Benzathine penicillin G
- -inhibits cell wall synthesis
- -IM
2. Doxycyline
- -tetracycline (inhibit 30s and protein synth)
3. Azithromycin
- -macrolide, inhibits 50s
**test for HIV
114
Micro pharm: What is treatment for N. gonorrhea?
1. Ceftriaxone
- -3rd gen cephalosproin
- -inhibits cell wall synth
+ Azithromycin
115
Micro pharm: What is an alternative treatment for N. gonorrhea?
Doxycycline x7 days
116
Micro pharm: What is the treatment for C. trachomatis?
1. Doxy
- -tetra
- -30s
OR
2. Azithromycin
- -macrolide
- -pregnancy *
117
Micro pharm: What is the treatment for Group B strep (agalactiae)?
a. ceftriaxone
b. Penicillin
c. Doxycylin
d. Penicillin, Clindamycin or Vancomycin
D
1. Penicillin G (amox)
(inhibits cell wall synth)
2. Penicillin allergy: Clindamycin
- -inhibits protein synth;
* *inc. risk C. diff
3. Vancomycin if not sensitive to Clinda
118
Micro pharm: what is the treatment for T. vaginalis?
1. Metronidazole
--nitroimidazole
MOA: nitrogroup is reduced by protozoal enzymes producing toxic, nitro free ROS = damage DNA and proteins
119
Micro pharm: What is the treatment for T. gondii?
a. Spiramycin
b. Ketoconazole
c. Pyramethamine
d. Albendazole
1. < 18 weeks:
- -Spiramycin (macrolide; inhibits protein 50s)
2. > 18 weeks:
a. Pyramethamine (inhibits dihidrofolate reductase)
+ Sulfadiazine (inhibits dihidrofolate synth)
+ Leucovorin (active folic acid; rescue from hemotoxic effects of pyramethamine)
120
Micro pharm: What is the treatment for candida albicans?
a. fluconazle
b. doxycyclin
c. azithromycin
d. permethrin
1. Fluconazole
--inhibits enzyme that converts lanosterol to ergosterol
* topical in pregnancy
* may require 2-3 doses
121
Micro pharm: What is the treatment for HSV?
a. acyclovir
b. fluconazole
b. remdesivir
d. ceftriaxone
1. Acyclovir
* nucleoside analog
* inhibits viral DNA pol
MOA: prodrug phosphorylated by viral thymidine kinase = activates host kinases = inhibit viral DNA polymerase
122
Micro pharm: What is the treatment for varicella?
a. acyclovir
b. remdesivir
c. ketoconazole
d. metronidazole
1. Acyclovir
--nucleoside analog
MOA: inhibits DNA pol
NOTE: varicella pneumonia in pregnancy is medical emergency -- I.V.
123
Micro pharm: What is the treatment for CMV?
anti-virals not indicated
124
Micro pharm: What are the adverse effects of
1. Penicillin
2. Azithromycin
3. Ceftriaxone
4. Doxycyclin
1. Penicillin
- -GI, HSR
2. Azithromycin
- -GI
3. Ceftriaxone
- --GI, HSR,
- -yeast infection
4. Doxycyclin
- -phototoxicity
- -discolored teeth
- -GI upset
125
Micro pharm: What are the adverse effects of
1. Spira
2. Pyramethamine + sulfadiazine
3. Acyclovir
4. Metronidazole
5. Fluconazole
1. Spira
- -GI
2. Pyramethamine + sulfadiazine
- -folate deficiency
- -hematologic (leucovorin helps)
3. Acyclovir
- -GI, HA, rash
4. Metronidazole
- -GI
5. Fluconazole
- -drug interactins (P450)
126
Micro pharm: Cisplatin is used in the treatment of squmaous cell carcinoma
What is its mechanism of action? What are its adverse effects?
1. MOA
- -DNA alkylating agent
- -crosslinks DNA via N7 guanine
* platinum derivative
2. Adverse
- -
127
Micro pharm: Fluroruracil is a DNA synthesis inhibitor that is used for the treatment of squamous cell carcinoma (vulva, vagina, cervix). What is its mechanism of action?
a. inhibits thymidylate synthesis
b. crosslinks DNA via N7 guanine
c. inhibits estrogen synthesis
A
Pyrimidine antagonist
- -inhibits thymidylate synthesis
- -gets incorporated into RNA
128
Micro pharm: Hormone replacement therapy targeting breast tissue include Tamoxifen and Anastrozole. What are their MOA's?
1. Tamoxifen
- -estrogen antagonist (binds E2; SERM)
2. Anastrozole
- --aromatase inhibitor
- -inhibits E2 synthesis
129
Micropharm: Targeted therapy for the breast includes
1. Trastuxumab
2. Lapatinib
3. Everolimus
4. Palbociclib
Match the drugs with their correct MOAs (below)
a. ab to HER-2 neu
b. tyrosine kinase inhibitor
c. mtor kinase inhibitor
d. CDK 4/6 ibhibitor
1. Trastuxumab
- -ab to HER2-neu receptor
- -(HER2 neu is tyrosine kinase involved in cell proliferation
2. Lapatinib
- -tyrosine kinase inhibitor
- -inhibits intracellular phosphorylation in HER2/neu signalling
3. Everolimus
- -mTOR kinase inhibitor
- -inhibits cell cycle progression
4. Palbociclib
- -cycline dependent kinase (CDK 4/6) inhibitor
- -prevents cell cycle progression
130
Micro pharm: Cytotoxic agents (ACT therapy) in the Breast include:
1. DOxorubicin
2. Cyclophosphamide
3. Paclitaxel
_________ is an antibiotic that inhibits topoisomeraseII. It binds DNA and causes inhibiton of DNA synthesis. It also binds the cell membrane to alter the fluidity and ion transport. Generates ROS
Doxorubicin
* cyclophosphamide: DNA alkylating agent
* Paclitaxel (Taxane): inhibits tubulin depolymerization (mitotic inhibitor)
131
Micro pharm: Agents used for ovaries/fallopian tube:
1. Carboplatin
2. Paclitaxel
It is similar to cisplatin but less toxic. What is the MOA?
DNA alkylating agent
* inorganic platinum derivative
* cross-links DNA via interaction at N7 guanine
132
Micro pharm: Nearly all anti-neoplastic drugs cause acute nausea/vomiting and delayed alopecia + myelosuppression.
List the adverse effects seen with:
1. Cisplatin
2. Doxorubicin
3. Cyclophosphamide
4. Fluoruracil
5. Anastrozole
1. Cisplatin
- -renal toxicity
- -less with carboplatin
2. Doxorubicin
- -cardiotoxicity
3. Cyclophosphamide
- -hemorrhagic cystitis
4. Fluoruracil
- -GI/oral ulcers
5. Anastrozole
- -hot flashes
133
Micro pharm: Micro pharm: Nearly all anti-neoplastic drugs cause acute nausea/vomiting and delayed alopecia + myelosuppression. Match the adverse effects with their respective drugs:
1. Tamoxifen
2. Trastuzumab
3. Lapatinib
4. Palbociclib
5. Everolimus
a. diarrhea, rash
b. bleeding, bruising, dizziness
c. hot flashes, hypercalcemia\'
d. heart failure, pulmonary tox
e. mouth sores, rash
1. Tamoxifen
- -hot flashes, hypercalcemia
2. Trastuzumab
- -chest pain, heart failure, pulmonary tox
3. Lapatinib
- -diarrhea, rash
4. Palbociclib
- -bleeding, bruising, dizziness
5. Everolimus
- -mouth sores, rash
134
Erectile dysfunction: Drugs for erectile dysfunction include:
1. PDE 5 inhibitors ("fils")
2. Vasoactive erectile agents
_____ are 1st line (oral drugs) for erectile dysfunction. They increase erectile function by preventing PDE-5 mediated inactivation of cGMP. This leads to SM relaxation, vasodilation, and inc. blood flow to the corpus cavernosum.
PDE 5 inhibitors
-Sildeniafil, Vardenafil, Tadalafil, Avanafil
135
Erectile dysfunction: PDE-5 inhibitors are metabolized by CYP3A4 enzymes in the liver.
Use of PDE-5 inhibitors in contraindicated in visual disorders and CV disorders. What are the side effects? Drug interactions?
1. Adverse
- -opthalmic/visual disturbances (rare)
- -priapism (rare)
- -anti-priapism
* avanafil = less side effects
2. Drug interactions:
a. vasodilators (nitrates)
- -inc. risk orthostatic hypotension and heart attack
b. CYP3A4 inhibitors
- -inc. side effects
*tadalafil - longest duration
136
Erectile dysfunction: Alprostadil is the 2nd line treatement of ED approved by the FDA.
It produces erection without sexual stimulation in < 10 minutes and can be combined with sildenafil for higher efficacy. How is it administered?
1. injected into cavernous tissue
| 2. Inserted (mini-suppository) into the urethra
137
Erectile dysfunction: Vasoactive erectile agents include: Phentolamine and Papaverine (bi-mix).
These are relatively effective in men with minimal ED, but not FDA approved. They are useful w/ px refractory to PDE-5 inhibitors.
True/False - Phentolamine promotes weak erectile activity when used alone, but potentiates the effects of papaverine and alprostadil when combined
True
* alprostadil + papaverine + phentolamine (tri-mix w/ inc. efficacy)
* tri-mix + sildenafil -- useful in px who don't respond to regular tri-mix or sildenafil alone
138
Erectile dysfunction: The MOA's of vasoactive erectile agents are (choose from below)
1. _____ inhibits PDE-5 and PDE 3/4 in SM.
2. _____ inhibits alpha-1 adrenoceptors
3. _____ (PGE1) activates prostaglandin E receptors
Each drug ultimately induces SM relaxation, increasing vasodilation and inc. erection.
a. papaverine
b. aprostadil
c. phentolamine
1. Papaverine
2. Phentolamine
3. Alprostadil
139
Erectile dysfunction: What are the adverse effects of Vasoactive erectile agents?
a. priapism
b. hypotension
c. hypertension
d. chest pain
1. Phnetolamine and Papaverine
- -hypotension
- -priapism (higher than PDE5Is)
2. Alprostadil
- -priapism (lower than papaverine)
140
Erectile dysfunction: Match the drug interactions with the correct drugs
1. Phentolamine + Papaverine
2. Aprostadil
a. orthostatic hypotension
b. heart attack
c. vasodilators
1. Phentolamine + Papaverine
- -Inc. risk orthostatic hypotension and heart attack
* *avoid
- -Cx: CV disorders
2. Aprostadil
- -Ix: Vasodilators
- -Cx: Urethritis
141
Hypoactive Sexual Desire Disorder: Medications for HSDD include:
1. Flibanserin (oral)
2. Bremelanotide (injectable)
True/False - Both drugs are FDA approved for treatment in HSDD in pre-menopausal women. However, they are NOT approved for menopausal women, men, drug-decreased libido, or to enhance sexual performance.
True
142
Hypoactive Sexual Desire Disorder: Although the MOA of Flibanserin is unknown, it is believed that it acts to decrease glutamine release in the brainstem. This improves balance b/t excitatory (Inc. DA and NE) and inhibitory (Dec. 5HT) neurotransmission, leading to inc. sexual response.
What are adverse effects? Drug interactions? Cx?
1. Adverse:
- -Hypotension (syncope)
- -CNS depression
2. Drug Ix
AVOID: CYP3A4 inhibitors (liver metab; inc. risk hypotension and syncope)
AVOID: alcohol (inc. hypotension)
3. Cx
- -liver
- -CV
143
Hypoactive Sexual Desire Disorder: Medications for HSDD include:
1. Flibanserin (oral)
2. Bremelanotide (injectable)
_______ is an agonist of melanocortin receptors. It acts at MC4R in the brain, inc. DA release and activating DA receptors. It increases arousal response in women and men
Bremelanotide
144
Hypoactive Sexual Desire Disorder: What are the side effects of Bremalanotide? Drug interactions?
a. HTN
b. bradycardia
c. nausea
d. none
A-C
1. Adverse
- -Temporary HTN, bradycardia after injection
- -nausea during intercourse
2. Drug Ix
- -no problem with alcohol
3. Cx
- -CV and HTN
145
Genitourinary syndrome of menopause (GSM): GSM is due to decreased estrogen resulting in vaginal dryness and pain during intercourse.
Medications for GSM include:
1. Prasterone
2. Ospemifene
3. Estradiol (ultra-low dose)
Prasterone and Ospemifene are approved drugs for Tx moderate to severe painful sexual intercourse in pre-menopausal and post-menopausal women. ______ is a non-E2 drug, while _____ is a SERM that is used in cases of px refractory to prasterone and estrogen therapy
Prasterone and Ospemifene
1. Prasterone
- -non-E2 drug
2. Ospemifine (oral)
- -SERM
- -refractory to prasterone/estrogen therapy
146
Genitourinary syndrome of menopause (GSM): _____ (DHEA) is locally transformed into androgens and estrogens.
Estradiol improves vaginal lubrication, decreasing pain during sexual intercourse.
Prasterone/Estradiol
147
Genitourinary syndrome of menopause (GSM): Side effects of prasterone are fewer than oral DHEA and pose less cancer risk than oral estradiol.
There are no important drug interactions compared to oral DHEA or oral estrogens. What are Cx?
Vaginal bleeding
148
Genitourinary syndrome of menopause (GSM): Ospemifine is an antagonist at the _____ tissue (dec. proliferation) and an agonist at the ______ tissue (inc. proliferation).
1. antagonist at breast tissue (anti-estrogenic effects)
| 2. agonist at vaginal tissue (estrogenic effects - dec. vaginal dryness and atrophy)
149
Genitourinary syndrome of menopause (GSM): Ospemifene is metabolized via CYP enzymes in the liver.
What are side effects, drug interactions and Cx?
1. Adverse
- -vaginal discharge, hot flashes (common)
- -CV problems, blood clots (less common)
2. Ix
- -don't use with oral estrogens
3. Cx
- -vaginal bleeding
- -CV problems
- -pregnancy
150
Summary:
1. ED drugs
2. Painful sexual intercourse in women
3. HSDD in women
1. ED
- -1st line: PDE 5 inhibitors
- -2nd line: Alprostadil (can be combined w/ papaverine, phentolamine or sildenafil
2. Painful intercourse
- -Prasterone (DHEA)
- -Ospemifene (SERM)
3. HSDD
- -Filbanserin (5HT agonist/antagonist)
- -Bremelanotide (MCR agonist)
151
Male Histo: The penile urethra is the conduit for urine and semen.
During erection, there is increased pressure on the veins preventing backflow.
True
152
Male Histo: The majority of the body of the penis has no muscle except muscle in the wall of the blood vessels. At the distal end of the penis, is the corpus spongiosum, erectile tissue that expands to form the head of the penis (glans).
True/False - The corpus spongiosum and the corpus cavernosum are both erectile tissue surrounded by dense CT (tunica albuginea).
True
spongiosum: ventral; contains penile urethra and forms glans
cavernosum (x2): dorsal
153
Male Histo: The root (base) of the penis is composed of
1. Crus penis
2. Ischiocavernosus
3. Bulbospongiosus
The crus penis serves as the attachment site of the body of the penis, while the ischiocavernosus and bulbospongiosus are SK muscles that, when contracted, compress erectile tissue, facilitating urination, ejaculation and erection. What is the innervation of these muscles?
Perineal nerve
| somatic branch pudendal nerve
154
Male Histo: The nerves of erection and ejaculation include:
1. Pudendal nerve (S2-S4)
2. Perineal nerve (S2-S4)
3. Cavernous nerves from prostatic plexus (S2-S4)
_____ becomes the dorsal nerve of the penis, providing sensory and SNS innervation to the skin and glans of the penis
Pudendal
*relays sexual stimulation to CNS inducing contraction of bulbospongiosus muscle
155
Male Histo: The nerves of erection and ejaculation include:
1. Pudendal nerve (S2-S4)
2. Perineal nerve (S2-S4)
3. Cavernous nerves from prostatic plexus (S2-S4)
_____ is a branch of the pudendal nerve that innervates the bulbospongiosus muscle.
Perineal
156
Male Histo: The nerves of erection and ejaculation include:
1. Pudendal nerve (S2-S4)
2. Perineal nerve (S2-S4)
3. Cavernous nerves from prostatic plexus (S2-S4)
____ provides PNS innervation and innervates the helicine arteries. It innervates erectile tissue, facilitating erection. It is historically damaged during prostatectomy (leading to ED)
Cavernous nerves
*induce contraction of urethral muscle; blood flow into erectile tissue of penis
157
Male Histo: Describe the anatomy of Ejaculation
SEVEN UP
1. Sperm (produced in testes)
2. Efferent ducts -- Epididymus (stored)
3. Vas deferens (upon ejaculation)
4. Ejaculatory duct
5. Prostatic Urethra
Point N Shoot
SNS: L1-L2 (emission/closes Internal Urethral Sphincter); ejaculation (sympathetic and somatic)
158
Male Hissto: Ejaculation occurs because of
1. CLosure of the urethral sphincter
2. Contraction of external urethral sphincter muscle
3. Contraction of bulbospongiosus muscles
1. Neck or urinary bladder
- -SNS (L1-L2)
2. EUS
- -somatic (s2-S4)
3. Bulbospongiosus
- -Pudendal (somatic)
159
Male Histo: Arterial supply to the penis arises from the
1. Internal pudendal artery branches
2. Deep arteries of the penis branches
The branches of the internal pudendal artery supplies what structures? Deep arteries?
1. Internal pudendal branches
- -corpus cav and sponge, spongy urethra, penile skin
2. Deep branches into:
- -central artery -- helicine
- -supply erectile tissue
160
Male Histo: Venous drainage of the penis occurs via
1. Cavernous spaces (via venous plexus) --- Deep dorsal vein of penis --- prostatic venous plexus ---
2. Skin and Subcu --- superficial dorsal vein -- superficial external pudendal vein
* during erection blood fills sinusioids = compress veins
161
Male Histo: The penis has 3 masses of erectile tissue:
1. Corpus cavernosum (x3; dorsal)
2. Corpus spongiosum (surround urethra)
3. Tunica albuginea (fibroelastic layer)
True/False - Venous spaces within the cavernosusm and spongiosum are lined with endothelium and trabeculae w/ SM.
True
*tunica albuginea surrounds erectile tissue
162
Male Histo: Innervation of the penis involves PNS and SNS impulses.
1. PNS stimulates _____ of SM, dilates helicine arteries and enables erection
2. SNS constricts helicine arteries and trabecular SM, ______ flow into the sinus, and releases compressive pressure on veins (allowing blood flow).
1. Relaxes SM
- -compress dorsal veins against tunica albuginea
- -erection
2. Ejaculation --
- -dec. blood flow into sinus
- -veins drain blood from tissue
163
Male Histo: Erection occurs due to the relaxation of SM in the penis.
1. ____ neurons (cavernous/dorsal penile nerves produce NO
2. PNS neurons (cavernous nerves) release _____
3. Ach binds muscarinic receptors on endothelial cells, activating eNOS and inc. NO in endothelial cytoplasm.
4. NO diffuses from the endothelial cell. into the ____ cell, activates guanylate cyclase (which converts GTP to cGMP), and increases Ca storage and muscle relaxation
1. Nitregic neurons
2. Ach
3.
4. SM cells
164
Pap Smear: Guidelines for pap smears are age dependent:
1. < 21
2. 21-29
3. 30-65
4. > 65
1. No pap smear
2. Cytology alone, every 3 years
- -maybe reflex HPV (reflex is NOT co-testing)
3. Co-testing every 5 years
- -co- cytology + HPV testing
4. May stop screening if last 10 years adequate and negative
* ASCCP
* individualized approach
* HPV alone NOT recommended for any age group
165
HPV vaccines:
1. Bivalent
- -cervarix (16, 18)
2. quadrivalent
- -gradasil (6, 11, 16, 18)
166
Microbes (Vaginal discharge): History is important:
1. Medial (diabetes)
2. Recent/current meds
3. Sexual behaviors
4. Vaginal hygiene practices
5. Cyclic
How do you Dx
1. Wet prep
2. vaginal pH
3. Whiff test, KOH
167
Microbe that causes frothy, foamy, and strawberry cervix
Trich
Tx: metronidazole
168
PID criteria: Minimum criteria is cervical motion tenderness, uterine or adnexal tenderness on bimanual exam.
What is specific Dx criteria?
1. other signs pelvic infection (chlamy/gonorrhea)
2. fever > 101
3. elevated CRP, ESR
Tx: Ceftriaxone + Doxy (immediate treatment)
169
True/False - Long acting reversible contraception is number one choice for teens
true
Cx for hormonal bc: DVT, cancer, liver, cardiomyopathy, migraines iwth aura, stroke, smoking (relative)
