womens repro Flashcards
Genital human papillomaviruses (HPVs)
- role of early genes?
- role of late genes?
- common ‘low risk’ strains? 2
- common ‘high risk’ strains? 2
early genes:
- subvert host cell’s replicating apparatus to benefit virus
late genes:
- package virons so they can be expelled to infect other cells
low risk:
- cause benign genital warts (if anything)
- 6 + 11
- “6:11am is an annoying time to wake in the morning but not catastrophic”
high risk:
- can lead to cervical cancer
- 16 + 18
- “average age for people to loose thei virginity is between 16-18, promiscuous sex increases change of cervical cancer”
nb types 16 + 18 are included in HPV vaccine, but only cause 70% of cervical cancers so can still get cervical cancer if you’ve been vaccinated!
what are the 2 HPV vaccines given in the UK, what is each effective against + which is used now?
cervarix
- against 16 + 18 ONLY
- “just protects against CERVical cancer, not warts too”
- initially given from 2008 (incl catch-up)
gardasil
- against 6, 11, 16 + 18
- “GuARDs against both cancer + warts”
- used from 2012 onwards
nb types 16 + 18 are included in HPV vaccine, but only cause 70% of cervical cancers so can still get cervical cancer if you’ve been vaccinated!
what is the mechanism by which ‘high risk’ HPVs increase the risk of cancer?
‘high risk’ HPVs intergrate their DNA into host’s chromosome
as a byproduct of this process…
- E6 (binds to + inactivates P53)
- E7 (binds to RB1 gene product)
… are upregulated
P53 triggers apoptosis in response to bad DNA damage
RB1 is a tumour suppressor gene
this all -> increase risk of cancer!
vulval intraepithelial neoplasia:
- what is it?
- 2 different types? (incl cause, who affected)
a precancerous condition which often results in cancer of the vulva if not removed (progression to invasive cancer = 5% in treated women + 85% in untreated women)
classical/warty/baseloid:
- related to HPV infection
- younger women
- graded VIN 1-3
differentiated VIN
- associated with chronic inflammatory skin conditions (eg lichen sclerosus)
- older women
- not graded
- much harder to diagnose + treat
who is invasion of VIN most likely to occur in? 3
- postmenopausal women
- immunocompromised (incl local due to smoking)
- young, postpartum women (ie after give birth)
what is the most common type of vulval cancer?
what is it associated with? 2
what lymph nodes does it tend to spread to first?
what type of lymph node biopsy is done? why?
squamous cell carcinoma
- ‘high risk’ HPV infection
- inflammatory dermatoses (eg lichen sclerosus)
“lichen on your vag”
inguinal lymph nodes
sentinel node biopsy
- find node that stuff drains to first (sentinel)
- do this using radioactive tracer
- biopsy just this lymph node, if negative, likely all will be
- done instead of taking out all lymph nodes which results in lymphoedema in distal limb!
what staging system is normally used for gynae cancers?
FIGO system
not TNM
what two cancers each make up 5% of vulval tumours?
- age affected?
- prognosis?
malignant melanoma:
- 50-60 years
- lymph node/metastasis common -> poor prognosis
Paget’s disease:
- mean age 80
- tend to recur following excision (as doesn’t have well defined edge)
Paget’s disease:
- what is it?
- what is it often mistaken for?
- difference between nipple + vulval?
a type of skin lesion which is: - pruritic - burning - often red/inflammed it is a potentially pre-cancerous condition
often confused for eczema
- ALWAY biopsy ‘ezcema’ around nipple or vulva to check for paget’s as treating it with steroid cream (standard treatment for ezcema) could lead it to become cancerous
nipple (mammary) paget’s almost always has breast cancer under it whereas vulval (extra-mammary) doesn’t tend to and only rarely becomes adenocarcinoma
what changes to the epithelium of the cervix occur during a woman’s life?
where are cervical smear tests taken from? why?
columnar epithelium is in vagina, squamous epithelium is on skin
before puberty squamocolumnar junction is quite internal but then metaplasia occurs during menarche, produces a ‘transformation zone’ where squamous turns to columnar
after a woman’s menopause the transformation zone moves more internally into the vagina as more squamous cells are produced more externally
the transformation zone, as this is where dysplasia (and then cancer) almost always develops from
nb since the transformation zone in older women goes more internally, the smear test is more likely to miss it as it doesn’t go deep enough, so lots of false negatives in older women, hence why cervical smear less useful for older women
cervical intraepithelial neoplasia (CIN)
- what is it?
- grades?
- treatment for each grade?
a potentially premalignant dysplasia of cervical cells (normally in transformation zone)
CIN 1, 2 + 3
- indicate increasing dysplasia and likelihood of progression to invasion
CIN 1 - watch + wait (60% goes away)
CIN 2 or 3 - excision
cervical screening programme:
- age of first invitation?
- frequancy?
why no screening below this age of first invitation?
25
every 3 years until you’re 50
then every 5 years until your 65
rarely after 65, unless had abnormal tests
nb slightly different in different parts of UK
- high HPV carriage rate
- reactive changes
… mean this confuses results and there is a high false postive rate - unnecessary procedures to remove things have obstetric consequences
what is a colposcopy?
what is LLETZ?
examination of the cervix with a low powered stereoscopic microscope
cervix often painted with acetic acid to highlight potentially abnormal epithelium which can then be resected using a diathermy loop
this resection is called a large loop excision of the transformation zone (LLETZ) and is then studied by histopathologists
- nb side effect is large risk of miscarriages to future pregnancies
what is the algorithm followed in the case of abnormal smear tests?
smear tests test for abnormal cytology (ie dysplasia) AND HPV infection
if there is low level dysplasia WITHOUT HPV infection -> normal recall
if there is low level dysplasia WITH HPV infection -> refer for colposcopy
if there is high level dysplasia (with or without HPV infection) -> refer for colposcopy
risk factors for cervical squamous cell carcinoma:
- biggest?
- 2nd biggest?
- others? 6
high risk HPV
smoking (2nd) - causes local immunosuppression
- multiple sexual partners
- male partner with multiple partners
- young age at first intercourse
- high parity (given birth lots)
- low socioeconomic group
- immunosuppression
cervical adenocarcinoma
- cause?
- precursor?
- treatment?
- prognosis? why?
related to high risk HPV infection
cervical glandular intraepithelial neoplasia (CGIN)
treated same as squamous carcinoma or cervix (presention + spread are the same too)
stage for stage worse prognosis than squamous
- due to radiotherapy resistance
nb often found further up the cervix and so may produce false negatives on smear tests
cervical carcinoma:
- treatment?
- lymph nodes commonly metastasise to?
depends on FIGO stage
- from just LLETZ to varying levels of chemo + radiotherapy
nb try to avoid chemo/radiotherapy in young woemn as reduces fertility
pelvic + para-aortic
endometriosis:
- what is it?
- symptoms? 6
- diagnosis?
- treatment?
ectopic endometrial tissue (various theories as to aetiology) -> bleeding into tissue -> fribrosis -> pain
- dysmenorrhoea (painful periods) - main one!
- dyspareunia (painful sex)
- pelvic pain
- subfertility (if on ovaries)
- pain on passing stool
- dysuria
… depends where ectopic tissue is!
nb mismatch between how much endometriosis is present and severity of symptoms (can be asymptomatic)
laparoscopy used to diagnose
medical: - combined oral contraceptive - GnRH agonists/antagonists - progesterone antagonists surgical: - ablation - hysterectomy
endometritis:
- what is it?
- causes? 4
- symptoms? 5
- diagnosis? 2
- treatment? 3
- histological difference between acute + chronic?
inflammation of the endometrium
- pelvic inflammatory disease (caused by STIs like chlamydia/gonnorhoea)
- retained gestational tissue
- endometrial TB
- IUCD infection
- abdominal/pelvic pain
- pyrexia
- discharge
- dysuria
- abnormal vahinal bleeding
- biochemistry/microbiology
- ultrasound
- analgesia
- Abx
- remove cause (eg coil or retained tissue)
acute = neutrophil dominant chronic = lymphocyte/plasma cell dominant
endometrial polyps:
- symptoms? 3
- diagnosis? 2
- treatment?
- prognosis?
often asymptomatic
- intermenstrual/post-menopausal bleeding
- menorrhagia
- dysmenorrhoea
- ultrasound
- hysteroscopy
depends (medical or surgical options available)
< 1% are malignant
- but tend to remove anyway, just in case
leiomyoma (uterine fibroids):
- what is it?
- risk factors? 5
- symptoms? 4
- prognosis?
benign tumours of smooth muscle of uterus
- genetics
- nulliparity (never had a baby)
- obesity
- polycystic ovary syndorme
- hypertension
often asymptomatic
- menometorrhagia (heavy periods w increased frequency)
- iron deficient anaemia (dt loss of blood)
- subfertility/preg problems (as can thin overlying endometrium)
- heaviness or pressure in lower abdo (eg bloating feeling)
good prognosis (only very rarely -> leiomyosarcoma) - leiomyosarcomas normally develop de novo (ie not from fibroids)
endometrial hyperplasia:
- what is it? mechanism?
- risk factors? 6
- types? 4
excessive endometrial proliferation
- due to a high level of unopposed oestrogen (ie RELATIVELY lower levels of progesterone, which antagtonises oestrogen)
anything that increases oestrogen:
- obesity (^oestrogen)
- exogenous oestrogen
- polycystic ovary syndrome
- oestrogen producing tumours
- tamoxifen (blocks E receptors in breast cancer, stimulates them in endometrium)
- HNPCC
- simple non-atypical
- simple atypical
- complex non-typical
- complex atypical
nb atypia matters more than simple/complex
nb hard to tell difference histoligically between non-atypical and normal proliferation during parts of menstural cycle
endometrial hyperplasia:
- symptoms? 3
- diagnosis? 2
- treatment? 3
- prognosis?
abnormal bleeding
- inter-menstural bleeding
- post-coital bleeding (bleeding after sex)
- post-menopausal bleeding
- ultrasound
- hysteroscopy +/- biopsy
medical (if patient young + wants kids): - IUS - progesterone surgical (if wants no more kids): - hysterectomy
often develops into endometrial adenocarcinoma
endometrial adenocarcinoma:
- symptoms? 4
- stagingsystem used?
- treatment?
abnormal bleeding: - post-menopausal - inter-menstural - post-coital pain (if late stage)
FIGO (1-4)
medical: - progesterone surgery - hysterectomy adjuvent therapy - chemo - radio`
nb this is most common kind of endometrial MALIGNANT neoplasm
polycystic ovary syndrome:
- what is it?
- levels of LH and FSH?
- risk factors? 3
- diagnostic criteria?
a syndrome due to high androgen (eg testosterone) levels in women
- low FSH
- high LH
- family history
- obesity
- diabetes/metabolic syndrome
Rotterdam criteria: have 2/3 of:
- hyperandrogenism
- polycystic ovaries (on ultrasound)
- irregular periods (>35 days apart)
polycystic ovary syndrome:
- symptoms? 6
- treatment?
- can lead to? 2
nb a lot are asymptomatic
- irregular periods (or none)
- difficulty concieving
- excessive hair growth
- weight gain
- thinning hair + hair loss from the head
- oily skin/acne
lifestyle: - weight loss (has huge effect) medical: - metformin - oral contraceptive pill - clomiphene (-> upregulation of FSH) surgical: - ovarian drilling
- infertility
- endometrial hyperplasia/adenocarcinoma
what are the two types of (female) gonadal failure? (both names!)
- symptoms? 2
- investigations? 2
- treatment? 2
HYPERgonadotrophic hyponadism (primary hypogonadism)
- primary failure of gonads
- high GnRH
HYPOgonadotrophic hypogonadism (secondary hypogonadism)
- hypothalamic/pituatory failure -> gonad failure
- low/no GnRH
- amenorrhoea/absent menarche
- delayed puberty
- hormonal profiling
- karyotyping
difficult to treat:
- address cause
- hormone replacement therapy
Hypergonadotrophic hypogonadism:
- congenital causes? 2
- acquired causes? 4
aka primary hypogonadism
congenital:
- turner syndrome (XO)
- klinefelter’s syndrome (XXY)
acquired:
- infection
- surgery
- chemo-radiotherapy
- toxins/drugs
hypogonadotrophic hypogonadism:
- acquired causes? 3
aka secondary hypogonadism
Sheehan syndrome:
- lots of blood loss (eg in complicated preg) -> hypovolemia -> ischaemic damage to pituatory gland -> secondary gonadal failure
brain injury
- eg one which ->severing of pituatory stalk so hypothalamus can’t signal to pituatory
pituatory tumours
3 broad types of ovarian tumours?
which is, by far. most common?
surface epithelial tumours
- 90% (most common)
- nb they think these may actually originate in fallopian tube…
sex-cord stromal tumours (supportive cells)
germ cell tumours (‘the egg’)
nb epithelial tumours are always more common than non-epithelial ones as the cells are reproducing faster
germ cell tumours:
- germinomatous? 1
- non-germinomatous? 3
say malignant/benign + whether chemosensittive for each
dysgerminomas
- germinomatous
- malignant
- chemosensitive
teratomas
- non-germinomatous
- almost always benign in women
- often malignant in men
yolk sac tumours
- non-germinomatous
- malignant
- chemosensitive
choriocarcinomas (‘trying to be’ a placenta)
- non-germinomatous
- malignant
- often unresponsive to chemo
sex cord stromal tumours:
- incidence?
- benign/malignant?
- prognosis?
rare
almost always benign
however often produce androgens or oestrogen -> hormonal problems
meig’s syndrome:
- what is it?
- clinical signs? 3
- how is it treated?
paraneoplastic syndrome resulting from a benign sex cord stromal tumour
- ovarian tumour
- pleural effusion (almost always on right side)
- ascites
nb mechanism is unknown
remove the tumour + will resolve (may need to drain effusion as well!)
risk factors for all types of ovarian cancer? 8
- family history
- lynch syndrome (HNPCC)
- PMHx of breast cancer
- smoking
- oestrogen only HRT
- obesity
- increased age
- nulliparity (not giving birth)
“simply speaking, the more ovulation there is during a lifetime, the greater the risk of ovarian neoplasm, benign or malignant! so anything that increases total number of ovulations is an increased risk and anything that reduces that number is protective”
protective factors for all types of ovarian cancer? 3
- oral contraceptive pill
- breastfeeding
- hysterectomy
what are the symptoms of all types of ovarian cancer? 6
non-specific symptoms!!
- pain
- bloating
- anorexia (loss of appetite)
- weight loss
- PV bleeding
- urinary frequency
what is a krukenberg tumour?
a primary cancer of the GI tract that has metastasised to the ovaries and can often clinically present first in the ovaries
what % of women will get breast cancer in their life?
breast cancer screening:
- what age?
- how often?
1 in 8
50 -70 (trial extension 47-73)
mammogram every 3 years
fibrocystic change:
- what is it?
- risk factors?
- lifetime prevelence?
- risk of breast cancer?
- look on mammogram?
constellation of different benign changes in the breast tissue
- can form a lump, be associated with calcium + mimic cancer
increased exposure to oestrogen (same as breast cancer)
about 70% of women will get at some point, a common incidental finding
no increased risk
- except if family history of breast cancer
speccy bits of calcification
fibroadenoma:
- what is it?
- clinical characteristics? 2
- age group affects?
benign well-defined lesion showing a co-proliferation of ducts + connective tissue
- lump (with well defined edge)
- mobile/not tethered (no dimples formed)
women 10-40 (rarer after 40)
Risk factors for breast cancer? 9
linked to high oestrogen exposure
- early menarche
- late menopause
- oral contraceptives
- HRT (for menopause)
- nulliparity (not giving birth)
- alcohol
- obesity (esp post-menopause)
- increased age
- family history/genetics
nb childbearing + breast feeding reduce risk
DCIS:
- what is it?
- treatment?
ductal carcinoma in situ (in breast)
- the stage of a cancer before it invades (it will do if not removed)
wide local excision using ultra-sound guided wire
what 2 types of hormonal cancer treatment is given to patients with breast cancers?
when are they given?
if HER 2 positive, give herceptin
if oestrogen receptor positive, give tamoxifen
what diagnostic protocol is followed in diagnosing breast cancer? what does it involve?
the ‘triple assessment’
- does it CLINICALLY seem like cancer?
- does it RADIOLOGICALLY look like cancer? (lots of calcification)
- does it PATHOLOGICALLY look like cancer? (using ultra-sound guided biopsy)
diagnosis is only confirmed or rejected if all three agree!!
what are the 5 most common viral/bacterial causes of congenital abnormalities? (ie mother gets them when she is pregnant) and -> baby)
TORCH
T - toxoplasmosis O - other (eg syphilis, varicella zoster, parvovirus) R - rubella C - cytomegalovirus H - herpes simplex virus
what infections can a mother give to her baby as the baby is being born vaginally? (common ones) 4
- group B strep
- herpes simplex virsu (HSV)
- gonorrhoea
- chlamydia
nb also HIV and hep B - these can also transmit in utero or via breast milk
asymptomatic bacteriuria in pregnancy:
- if untreated, what % will get pyelonephritis?
- is it screened for?
symptomatic UTI in pregnancy is frequently preceded by asymptomatic bacteruria
untreated: 30% will get pytelonephritis
yes, screened in pregnant women and treated with Abx
evidence that this reduces risk of preterm delivery + low birth weight
which pregnant women should be given treatment (ie Abx) for group B strep (GBS)? 3
- women with a previous baby with neonatal GBS disease
- women with GBS in current pregnancy
- women who are pyrexial in labour
nb there is currently no screening programme for asymptomatic GBS in pregnant women
group B strep is a major cause of post-birth infections in babies - “B is for Babies”
what types of Abx are considered:
- safe during pregnancy? 2
- unsafe during pregnancy?3
safe:
- penicillins
- cephalosporins
unsafe:
- chloramphenicol
- tetracycline
- fluoroquinolones (eg ciprofloxacin)
what is the term given to inflammation of umbilical cord, amniotic membranes + placenta?
chorioamnionitis
aka intra-amniotic infection
risk factors for intra-amniotic infections? 6
- prolonged rupture of membranes (most common)
- amniocentesis
- cordocentesis
- cervical cerclage (cervical stitch to prevent preterm labour)
- multiple vaginal examinations
- bacterial vaginosis (via ascending infection)
what are the most common causative organisms in intra-amniotic infections?
what is the management for intra-amniotic infections?
- group B strep
- e coli
“B for baby”
Abx ASAP (ie before baby born) - deliver foetus as soon as it is viable!
puerperal endometritis:
- what is it?
- risk factors? 4
- possible complication?
infection of the womb during puerperium (delivery to 6 weeks post-delivery)
- caesarean section
- prolonged labour
- prolonged rupture of membranes
- multiple vaginal exams
puerperal sepsis
puerperal endometritis:
- symptoms/signs? 6
- common causative organisms?
- treatment?
- fever
- uterine tenderness
- abdo pain
- purulent, foul-smelling lochia (the vaginal discharge after giving birth)
- increased white cell count
- general malaise
frequently mixed cause:
- e coli
- group B strep
(- group A strep)
broad spectrum IV antibiotics, continued till woman has been apyrexial for 48hrs
Early onset sepsis (EOS):
- present within?
- higher mortality in? 2
- normal causative organisms? 2
72 hours of birth (norm within 24hrs though)
- preterm babies
- babies with low birth weight
- group B strep (50%)
- e coli (25%)
late onset sepsis:
- who normally affect?
- norm causative organism?
- preterm babies/babies who have to be kept in neonatal unit for long time
- staph (norm hosp acquired, as opposed to from mothers genital tract)
what is the type of bacteria which causes the most major bacterial infections in children?
pneumococcus
what are signs/symptoms of otitis media in infants/young children? 7
- unusual irritability
- difficulty sleeping
- tugging or pulling at one/both ears
- fluid draining from ear
- fever
- loss of balance
- unresponsive to quiet sounds (or other signs of hearing loss)
what is the leading viral cause of acute resp infections in children?
respiratory syncitial virus (RSV)
bronchiolitis in children:
- symptoms?
- signs?
- cause?
- fever
- nasal discharge
- dry, wheezy cough
on examination:
- fine inspiratory crackles and/or high-pitched expiratory wheeze
almost always caused by viruses
pneumonia in children:
- symptoms in infants/young kids? 5
- symptoms in older kids? 7
infants/young kids
- fever (possibly preceeded by a viral URTI)
- breathlessness (nb rarely cough)
- poor feeding
- irritability
- sleeplessness
older kids:
- cough
- chest/abdo pain
(- plus above symtoms)
pertussis:
- another name for it?
- 3 stages of illness?
- vaccine?
whooping cough
- highly contagious bacterial infection
catarrhal phase:
- ‘cold-like’ (coryza, conjunctival irritation, occasionally a slight cough)
- 7-10 days
paroxysmal phase:
- rapid, forced expirations, followed by mgasping inhalation (the typical whooping sound)
- post-tussive vomitting is common
- 2-6 weeks
convalescent phase
- slow resolution of symptoms, vomitting stops, may still ‘whoop’, but cough less
- 1-4 weeks
all pregnant women now get booster vaccine
what causes gray baby syndrome?
if mother is given the Abx chloramphenicol whilst the baby is in utero
what is puerperal mastitis?
what is the most common cause?
post-delivery inflammation (norm due to infection) of the breast tissue
staph aureus
nb mothers should keep breast feeding as no risk to baby and may speed up mother’s recovery
what are the signs/symptoms of an infant with meningitis? 8
- fever
- irritability
- lethargy
- poor feeding
- high pitched cry
- bulging anterior fontanelle
- convulsions
- opisthotonus
nb non-specific clinical presentation
meningitis in infants:
- tend to be viral or bacterial?
- what is most common causative agent?
- how can you tell difference between bacterial + viral meningitis by lookong at CSF?
most commonly viral
enteroviruses (50% <3mths)
tends to be a lot more lymphocytes in csf in viral
symptoms of UTIs in infants? 4
- fever
- irritibility
- vomiting
- poor appetite
nb non-specific symptoms
symptoms of UTIs in older children? 5
- dysuria
- frequency
- urgency
- small volume of urine
- low abdo pain
how does NICE recommend you obtain a urine sample from an infant?
try to get a clean catch sample
- if not possible, use urine collection pad
(NOT cotton wool or sanitary towel etc)
if not possible:
- use catheter sample or suprapubic aspiration
meningococcemia symptoms in infants? 9
- fever
- non-specific malaise
- lethargy
- irritibility
- seizures
- vomiting
- meningism
- resp distress
- macpap or petechial rash
what is meningism?
set of symptoms which are normally caused by meningitis but there is no underlying meningitis
includes triad of symptoms:
- neck stiffness
- photophobia
- headache
impetigo:
- causative organisms? 2
- who most susceptible?
- treatment?
- management?
- staph aureus
- strep pyogenes
kids with underlying skin condition
topical antibiotics
don’t go to nursery/school
- very contagious
scarlet fever:
- causative agent?
- normally follows what?
- treatment?
group A strep
2-4 days post strep throat
penicillin
symptoms of scarlet fever? 8
- fever
- unwell
- sore throat
- unwell
- flushed face (but pale around lips = circumoral pallor) - rash may extend to body
- rough ‘sandpaper’ skin
- skin peeling (desquamation) - particularly on palms + soles of feet)
- white strawberry tongue
symptoms of measles? 5
- fever
- coryza
- conjunctivitis
- maculopapular rash
- koplik spots (on buccal mucosa)
measles:
- how long does rash last?
- when infective?
- how spread
- causative agent?
about 6 days
from 4 days before rash onset
person to person by direct contact with infectious droplets (or less commonly by airbourne spread)
measles virus
rubella:
- symptoms? 2
- how long does rash last?
- when infective?
- how spread?
norm present with few/no clinical symptoms
- fever
- pink maculopapular rash (starts on face then does downwards)
2-5 days (‘3-day measles’)
infective up to 5 days before rash
transmitted via contact with infected nasopharyngeal secretions
what is the most common neoplasm of the uterus?
leiomyoma (aka fibroids)
nb neoplasms are just new growths (ie can describe benign or malignant growths)
why does obesity, especially post menopause, increase your chances of many gynae cancers?
obesity means you get peripheral conversion of adipose tissue to oestrogens (especially in post-menopausal women - as no progesterone to oppose it)
unopposed oestrogen = a carcinogen
what is a serum marker used to aid the diagnosis of ovarian cancer?
CA-125
“ca = CAncer, 25 is our family house number and our family came from ovaries, and we are all ONE happy family- wow I’m tired.”
nb this has reasonably low sensitivity and specificity though!
