Week 5 - Female Genital System Flashcards
Identify the common causes of vaginal bleeding/discharge.
Vaginal bleeding:
• Pre pubertal - trauma, foreign body, rare malignancy (sarcoma botryoides).
• Pregnancy - placenta praevia, miscarriage, ectopic pregnancy.
• Post-coital bleeding - lesions of cervix (carcinoma).
• Post-menopausal - uterine lesion (endometrial polyp/carcinoma).
• Abnormal menstruation - DUB - psychological, hormonal, dysfunction, haemostasis disorder. Local - infection, fibroids, polyps, endometriosis.
• Pain - uterine spasm, obstruction, adenomyosis, PID, tubal pregnancy, torsion.
Discharge:
• White, cheesy - Candida.
• Clear/watery - Trichomonas, gardnarella, Chlamydia, eczema.
• Pus/purulent - Gonococcal, bacterial.
• Haemorrhagic - Infections, trauma, malignancy.
Describe the normal anatomy of the female genital system.
• Uterus and ovary come from 2 different embryonic structures - Müllerian duct and Mesonephric duct.
- Mesonephric duct gives rise to ovary.
- Müllerian duct gives rise to tubes, uterus, vagina, cervix.
• All people female by default.
• SRY gene on Y chromosome → male.
- If have Y chromosome and SRY gene not functioning → female.
Outline the menstrual cycle.
• Hypothalamus → GnRH increases before ovulation (follicular phase).
• Pituitary → FSH and LH surge → follicles rupture and release ova at this point.
• Ovarian hormones
- Oestrogen gradually increases.
- Inhibin is the opposite of oestrogen.
- Following ovulation is the luteal phase.
• Endometrium goes through stages of proliferation and menstruation.
• Basal body temperature increases after ovulation.
Describe the transformation zone.
- Transformation zone - site of cervical cancer
- Pre-pubertal - endocervix is inside, vagina and cervix covered by stratified squamous epithelium.
- During pubertal reproductive phase - the endocervix comes out - the columnar cells which are very sensitive cells are exposed. Also at this time, sexual activity exposes further infections to this zone.
- Exposed endocervical cells undergo metaplastic change to become stratified squamous epithelium from columnar epithelium. This zone is known as the transformation zone - site of cervical zone.
Outline the normal cervix.
- Endocervix - columnar epithelium.
- Ectocervix - squamous epithelium.
- Abrupt transformation from endocervical columnar epithelium to squamous epithelium.
- High vaginal smear → infections.
- Cervical smear (transformation zone) → cancer.
- HPV, the causative agent of cervical cancer has an affinity for the immature squamous cells of the transformation zone.
Outline vulva and vaginal disorders.
- Many different disorders.
- Commonest inflammations - sexually transmitted
- Cancers can also occur - less common.
- Young children can develop high grade sarcoma - CT tumour known as sarcoma botryoides.
- Bartholin cyst - obstruction and secondary infection of vaginal glands.
- Adenosis - chronic inflammation of vagina leading to increased mucous gland
Outline vulvo-vaginitis - vaginal discharge
• Common - infection. Present as vaginal discharge. Can be simple inflammation (clear fluid), slighty turbid or cheesy discharge.
• Contact dermatitis:
- Urine, soaps, antiseptics, deodorants, creams, foreign body etc. oozing and crusting papules (children common).
• Infections:
- Chlamydia - asymptomatic, clear to pus discharge.
- Herpes - HSV 1 or 2, genital herpes - vesicles.
- Candida - Pregnancy/DM - thick, white cheesy discharge.
- Trichomonas - watery pale - yellow pus discharge.
- Syphilis - primary - chancre, secondary, tertiary.
- HPV - condyloma accuminata, wart.
• Inflammations and atrophy:
- Lichen sclerosis - atrophic, hyperplastic.
Identify the investigations for STIs.
• Tested for multiple STI organisms - Gonorrhea, Chlamydia trachomatis, Trichomonas vaginalis, Candida, syphilis and HIV infection. Mycoplasma genitalium (recurrent).
- Usually completed as a battery of multiple organisms - multiple organisms can occur together.
• Endocervical and high vaginal swab (in case of males - uretheral swab).
• Transport media UTM-RT (universal) sucrose phosphate. Minimal Transport time, store samples at low temp.
- Usually sent in transport media containing sucrose.
• Nucleic Acid Amplification test (NAAT) is now standard molecular genetic technique (PCR, RT-PCR etc.) detects pathogen earlier than antibody tests (window period).
- Another name for PCR, reverse transcriptase PCR.
- Now known as NAAT - standard.
- Detects pathogens much earlier than antibody tests as antibodies take time to develop (known as window period)
- Swab is rotated high in vagina fornix and sent in transport media.
Outline cervicitis.
- Inflammation of cervix.
- Common - secondary to vaginal infections.
- STD - Gardnerella, Chlamydia, Trichomonas, Candida etc.
- Plenty of inflammatory cells in the PAP smear.
Outline endocervical polyps - benign.
• Plenty of inflammatory cells in the PAP smear.
- Chronic inflammation usually produces polyps - mucosal gland hyperplasia with plenty of inflammatory cells (similar to chronic rhinitis producing nasal polyps).
Outline Chlamydiasis.
• Common (developed world), asymptomatic 80%.
- Pus is not common presentation - can be clear fluid or pus.
• Common cause of long term complications - PID, infertility, ectopic pregnancy etc.
• No discharge or clear/pus discharge (less irritation/itching - more asymptomatic).
• Cytoplasmic reticulate bodies - seen within cytoplasm of epithelial cells.
- Clinically do NAAT test.
Outline Mycoplasma Genitalium.
• Similar in clinical features.
- Asymptomatic.
• No cell wall → resistant to penicillin.
- Organisms have no cell wall → resistant penicillin - chronic/recurrent STDs common.
• Lab diagnosis - NAAT (nucleic acid amplification test).
Outline Trichomonas vaginitis/cervicitis
• Flagellate protozoa - Trichomonas vaginalis (>50%).
- Cannot use antibiotics.
• Asymptomatic (<50%) to clear watery to white/yellow bubbly discharge, malodour, erythema, itching.
- Bubbles within the discharge is very typical.
• Increased pH → bacterial vaginosis. Strawberry cervix*
- Inflammation of cervix typical produces strawberry cervix - multiple erythematous spots.
• Produces proteolytic enzymes, complement, neutrophils.
- Breaks down mucosal defence → increased HIV and other STD infections in patients with Trichomonas.
• Increased HIV risk, PID and preterm birth.
- PID and preterm birth - long term complications.
• Urethra involvement common in males.
• Microscopy - parasites (protozoa) seen as flagellate leaf shaped cells → motile organisms.
Outline Candida vulvovaginitis - Thrush.
• Fungus - Candia albicans
• Pregnancy, diabetes, immunodeficiency, HIV.
- Very common in pregnant women.
• Itching, sore, burning. Bright red rash.
• Heavy, white, curd/cheesy discharge.
- Thick cheesy discharge.
• Vaginal swab/PAP smear - diagnosis.
• Branching hyphae and budding yeast forms.
- Very characteristic of the fungus.
Outline genital herpes.
• Commonly by HSV-2, HSV-1 increasing.
• Second common STI in Australia.
• Women, ~30 years, Indigenous.
- Women, reproductive age.
• Viral replication - peak in 3-4 days.
- Viral replications peaks 3-4 days after age.
• Large intranuclear inclusions (Cowdry A) and multinucleated giant cells.
- Large intranuclear inclusions - characteristic microscopy feature known as Cowdry A inclusions.
• Asymptomatic in majority → clusters of multiple, painful vesicles → ulcers.
• Tzanck smears of lesion simple (do not distinguish VZV and HSV infections).
- Scraping of lesions and taking fluid is known as Tzanck smears.
• NAAT test.
- Confirmatory test.
Outline syphilis.
Primary syphilis:
• Primary chancre - painless hard.
Secondary syphilis:
• Condyloma Lata - knob/wart like.
• Rash (palmar/plantar) - Erythemat/pigmented.
Outline Condyloma Accuminatum.
- Soft, moist, papillomatous/warty growth.
- STD - HPV serotypes 6 and 11.
- Low risk of malignancy.
- Microscopy - hyperkeratosis, papillary projections. Overgrowth of epithelium. Hyperview - perinuclear hallow known as koilocytes. Usually within basement membrane, do not spread (not a malignancy - benign tumour).
HPV cytologic features: • Koilocytosis* • Hyperkeratosis. • Parakeratosis. • Papillomatosis. • Dyskeratosis & Dysplasia. • Intact basement membrane.
Outline vulval disorders.
Carcinoma (of the vulva) and Paget’s disease
• Rare, similar to cervical cancer, HPV 16.
• 3%, starts as dysplasia (VIN)
- Vulva intraepithelial neoplasia.
• Slow growth. Size: <2cm better.
• Paget’s disease - same as breast.
- Eczematous lesion due to malignant cells spreading to skin.
Lichen Sclerosus et.atrophicus
• Immune, T cell mediated.
- Epidermis undergoes marked thinning.
- Atrophy.
Lichen Simplex Chronicus
• Sq. Hyperplasia - Chronic irritation.
- Opposite - excess proliferation of skin.
- Both present as whitish scar like patches. 2 conditions of epithelial disorder but not cancer.
- Hyperplasia.
Outline pelvic inflammatory disease.
- Chronic complication of many STDs (infections) - common being chlamydia.
- Organisms enter into the uterus and spreads through the fallopian tube into the peritoneal cavity → leads to chronic inflammation spreading to all the organs within the pelvis leading to chronic inflammation → pain, fever, mass (inflammatory granulation tissue), obstruction of fallopian tube leading to infertility.
- Inter organ adhesions due to chronic inflammations and scarring. Pelvic organs become one inflammatory mass.
- Can also occur secondary to endometriosis.
Outline cervical cancer.
• 1st → 13th common cancer (PAP screening).
- Use to be most common cancer in females.
- PAP screening - early detection of cancer.
• First cancer to get vaccine*
• Pap screening → decreased incidence 99%*
• ‘Squamous cell carcinoma’
• It is an STD - Human Papilloma Virus (HPV 16, 18).
- STD due to HPV.
• Aetiology: HPV + oestrogens + others.
• Prolonged pre-cancer dysplasia ~ 10y CIN (cervical intraepithelial neoplasia).
- Characterised by long pre-cancer dysplasia phase - ~10 years - known as CIN.
• Present asymptomatic/post coital bleeding*
• Dysplastic cells in pap screen ~2y*
- Dysplastic cells can be seen in pap smears more than 2 years earlier than the clinical cancer.
• Not all CIN progress to invasive cancer.
• LSIL <5%, HSIL >70% → ca.
- Low grade lesions - approx. 5% become malignant.
- High grade - 70% become cancers.
• 5y survival stage 1 >80%, stage 4 ~10%.
• Normal transformation zone → leading onto whitish plaques (leukoplakia with HPV infection) → high grade lesions (erythematous areas) → cancer (period of nearly 10-15 years minimum for developing the cancer).
Describe the aetiology of cervical cancer.
Aetiology (HPV + oestrogens + others)
• HPV - DNA virus (initiator - causes the mutation).
- Multiple partners - STI. Mucosal contact. Usually due to sexual exposure, mucosal contact is important.
- High risk - bind to cell DNA - 16, 18 (31, 33…). Many types of HPV - high risk types are where the viral DNA binds to cellular DNA to cause mutations (16 and 18). Many other subtypes - less common.
- Low risk free viral DNA - 6, 11 (42, 43, 44…)* Usually causes benign tumours because they don’t bind to the cellular DNA.
• Oestrogens - growth control hormones (promoter).
- Mutation (initiator) plus excess oestrogen (promoter) → cancer.
- Early menarche, late menopause, lack of pregnancy, hormone therapy obesity and hyper-oestrogenemia (endometrial polyps, hyperplasia etc.)
• Other factors
- Family history* - independent risk factor. Genetic factors less important compared to breast cancer.
- Smoking/other carcinogens (promoter)
- Other viral/mutations rarely.
Describe the structure of HPV.
- DNA virus.
- Capsid contains many proteins - gp120 and gp41 important.
- HPV vaccine manufactured by taking the segment of the DNA which produces the viral capsid in fungus → produces capsid proteins and empty viral capsids (covering of the virus without its DNA) → extracted as vaccine → induces immunity.
Describe the HPV vaccine.
• Since 1991 a series of research on papillomavirus. First anti cancer vaccine 2006. Australian of the year 2006.
• Vaccine has shown ~100% efficacy in the phase III human trial on over > 25,000 women.
• In 2006, FDA approved Merck’s vaccine, Gardasil a quadrivalent vaccine against strains 6, 11 (wart) and 16, 18 (Ca) of the HPV virus.
• HPV also causes cancer of oropharynx, vulva, vagina, penis, scrotum, rectum and perineum.
- Vaccine also prevents other HPV induced cancers.
Explain the pathogenesis of cervical cancer.
• HPV (DNA virus) is found in >99.7% of Ca.Cx.
• >100 types, transmit by mucosal contact (STI).
• 6 and 11 - benign warts/condyloma accuminatum, LSIL.
- Low grade dysplasia.
• 16 and 18: 70% cancer/CIN2 and 3 (HSIL).
- Rarely by other types 31, 33, 35, 39, 52, 56, 69 (many other types but not important).
- High grade.
• Virus infects immature squamous cells of transformation zone.
- Transformation zone around external os gets transformed to metaplastic squamous cells.
• Pathogenesis - HPV proteins E6 (bind p53) and E7 (bind Rb) tumour suppressor genes → loss of growth suppression → cancer.
• Normal → low grade → high grade dysplasia → cancer.
- Dysplastic changes (initially low grade then high grade) leading to cancer.
• Not all CIN progress to invasive cancer.
- Not all dysplasia leads to cancer - low grade lesions can revert back to normal. High grade → 70% cancer
• LSIL <5%, HSIL >70% → cancer.
• 6 and 11 - free DNA - infect many areas (vulva, vagina, cervix, skin, oropharynx) → leads to benign wart or condyloma accuminatum with mild dysplasia.
• 16 and 18 - bind to cellular DNA → cause mutations. E6 and E7 protein suppress tumour suppressor genes Rb and p53 → leads to tumour formation through the stages of low grade dysplasia, high grade dysplasia to cancer.
• Occasionally, due to unknown reasons, benign warts can become malignant.
*See diagram.
