Diseases 1

Question 1

What is polycystic ovary syndrome (PCOS)?

Answer 1

~ multiple causes, essentially ovulatory dysfunction and hyperandrogenism (male sex hormones) ~ implication on fertility, cycle, risk of metabolic syndrome (increased likelihood of dyslipidemia, DMIII (insulin insensitivity,), CV illnesses and endometrial carcinoma ~ one of the most common endocrine disorders

Question 2

Diagnostic criteria for PCOS?

Answer 2

think hirsutism, anovulation and polycystic ovaries 2 out of 3 of: * hyperandrogenism - “clinical or biochemical signs of hyperandrogenism”= either confirmed by test or through visual characteristics (excess hair with male distribution pattern = hirsutism, treatment refractory acne, etc) * menstrual irregularity - oligomenorrhea (< 9 periods /year or > 35 day cycle); amenorrhea (no periods for >=3 months) * polycystic ovary on imaging (transvaginal ultrasound or physical) (medium estrogen, low FSH and LH (reminder that low and medium esteren strongcks into pituitary so LFH and LH low, only in high estrogen do they become high) but NOT SPECIFIC TO PCOS!

Question 3

How do you evaluate for possible PCOS?

Answer 3

History ~ irregular menstruations ~ signs of hyperandrogenism Physical ~ see above Tests ~ total testosterone, can measure DHEA-S if want to r/o androgen-secreting tumour ~ ALWAYS hCG - r/o pregnancy ~ prolactin (r/o prolactinemia, prolactin down regulates FSH/LH), TSH (r/o thyroid disease, down regulates FSH/LH), FSH (ovarian insufficiency - b/c reacts to FSH first in follicular phase, and LH in luteal phase and just pre-ovulation) ~ transvaginal ultrasound also, patients with PCOS at risk of various metabolic things, so measure: ~ blood pressure ~ glucose = OGTT ideal, fasting can do too ~ lipid profile

Question 4

Tx for PCOS if pregnancy desired?

Answer 4

depends if pregnancy desired or not: #1 if pregnancy desired: clomiphene (claw + me + fan) citrate - estrogen receptor blocker at the level of hypothalamus and pituitary - even though medium levels of estrogen in PCOS (because each follicle produces some and multiple follicles present), LH and FSH not released for follicles to mature, so clomiphene citrate encourages brain to release FSH/LH to aid in ovulation idea: estrogen downregulates LH/FSH at pituitary (unless levels really high), block estrogen receptors -> LH and FSH released -> follicular cycle starts (LH already high, but byproduct here, need FSH at all cost) #2 letrozole “let-Roz(y)- O(vu)l(at)e” - off label, aromatase inhibitor, blocks conversion of testosterone into estrogen -> low estrogen -> FSH/LH release as above #3 FSH shots/IVF - expensive #4 ovarian drilling - essentially burning holes in ovaries if clomiphene fails and no money for IVF - shocks ovaries into decreased androgen production and gives about 6 months of ovulation, but risk of scarring ALSO: ~ weight loss really helps if overweight ~ metformin (due to insulin insensitivity frequent in PCOS) - not shown to be effective

Question 5

Tx for PCOS if pregnancy not desired?

Answer 5

1. exercise and weight loss if appropriate #2. oral birth control - especially important because unopposed estrogen (estrogen, but no ovulation, so no progesterone -> endometrium growing too much -> hyperplasia -> risk of CA -> need progesterone to shed uterine lining) also helps with acne and regulates periods do combined OC for that reason, if not wanting, do at least progesterone every few months to get menses to shed lining - progestin in divided doses alone will not reduce acne/or do contraception, unless taking continuous progesterone OC - “mini-pill” = MICROnor, IM Depo-Provera or Mirena IUD. also good for breastfeeding don’t forget to treat insulin resistance, dyslipidemia (statins), high bp and other conditions (usually metabolic) often present with PCOS

Question 6

Pathogenesis of PCOS?

Answer 6

Not known, but what we do know: EXCESS LH EXCESS ANDROGENS EXCESS INSULIN PREFERENTIAL RELEASE OF LH over FSH theca cells contain LH receptors -> LH -> androgen production (like testosterone) -> blood -> acne/hirsutism etc controlled by pulsatile GnRH release in the hypothalamus - this pattern seems to change in PCOS patients -> encourages preferential release of LH over FSH -> lack of ovulation (need FSH to stimulate follicular maturation) insulin -> somehow helps theca to increase androgen production insulin -> decreases sex hormone binding globulins (transport proteins for sex hormones in the blood, when attached to hormones, not bioavailable) -> increase free testosterone -> bioavailable

Question 7

MOA of clomiphene citrate?

Answer 7

clomiphene citrate = “Clomide” estrogen receptor blocker at the level of the brain (hypothalamus/pituitary) = FSH increased b/c negative relationship = GOOD unfortunately also blocks estrogen at uterine lining (not helpful b/c need healthy lining, not thin) = BAD cervix: makes cervical mucous thicker = BAD do you need more LH? nope, got tons, but do want FSH to kick start ovulation

Question 8

What is definition of menopause?

Answer 8

lack of menses for 1 yr - impossible to predict onset, diagnosis only post

Question 9

Types of menopause (physiological vs premature ovarian failure)?

Answer 9

physiological: average age 51 yrs in Canada (follicular atresia) premature ovarian failure: before age 40 (autoimnune, Turners, iatrogenic (surgical, radiation, chemo)

Question 10

Clinical features of menopause?

Answer 10

DUE to ESTROGEN DEFICIENCY: vasomotor instability: hot flushes, night sweats, sleep disturbances, nausea, palpitations (estrogen thought to influence heat sensors in hypothalamus and narrow range of temperature variations to which body doesn’t react) urogenital atrophy: vagina (prolapse), urethra, bladder dyspareunia (painful sex, often due to lubrication problems), pruritus, vaginal dryness, bleeding, urinary frequency, urgency, incontinence skeletal: osteoporosis, joint and muscle pain skin and soft tissue: thinning of skin and loss of elasticity, decreased breast size psych: mood disturbances, irritability, fatigue, decreased libido, cognitive (memory loss, etc) - treat with SSRI b/c estrogen decreases serotonin

Question 11

Investigations in menopause?

Answer 11

serum FSH/LH (how hard does brain have to work to produce follicles) = do day 3 if still cycling, FSH> LH, but may not be predictive b/c FSH variates a lot during the month, and esp. during menopause decreased levels of estradiol (later) diagnose by lack of periods for 1 year

Question 12

Treatment of menopause?

Answer 12

1 hormone therapy is first line, especially for estrogen withdrawal, like vasomotor instability can give SSRI for psychological symptoms vaginal atrophy: local estrogen cream, like Premarin, vaginal suppository (VagiFem), lubricants urogenital: lifestyle changes (bladder training, weight loss, surgery, estrogen) osteoporosis: 1000-1500 mg Ca, 1000 IU D, weight bearing exercise, no smoking, can give bisphosphonates like alendronate (Bone undergoes constant turnover and is kept in balance (homeostasis) by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss.) mood/memory: antidepressants CV: manage symptoms

Question 13

menopause pathophysiology?

Answer 13

degenerating granulosa and theca fail to react to FSH/LH from ant. pituitary -> less estrogen produced -> decreased negative feedback on hypothalamic-pituitary-adrenal axis (low estrogen -> increased FSH/LH ) -> increased FSH/LH but nothing to ovulate

Question 14

difference between perimenopausal, menopausal, premenopausal, postmenopausal

Answer 14

menopausal: permanent loss of ovarian follicular activity, 12 consecutive months of amenorrhea, avg. age 51 perimenopause: period of time prior to menopause, menopause and first year after menopause premenopause: the whole reproductive period prior to menopause postmenopause: from final menstrual period onward

Question 15

outline hormonal changes in menopause?

Answer 15

increased FSH and LH decreased estrogen decreased progesterone slightly decreased androgens (least affected since ovary does not produce a lot)

Question 16

what are menstrual changes during menopause?

Answer 16

cycles first get shorter than longer abnormal uterine bleeding depletion of primordial follicles amenorrhea eventually

Question 17

what is a LOOP cycle and a Lag cycle?

Answer 17

Loop cycle: Luteal Out Of Phase follicular event = premature formation of a follicle due to a major surge in FSH during the luteal phase lag cycle - long follicular phase with aberrant folliculogenesis (high E low P) cycle changes very typical in menopause

Question 18

Outline classification of abnormal uterine bleeding: PALM COEIN

Answer 18

STRUCTURAL CAUSES (PALM) ~ Polyps (endometrial or cervical) ~ Adenomyosis (endometrial tissue grows into muscular layer of the uterus) ~ Leiomyoma = fibroids (submucosal worst) ~ Malignancy/ hyperplasia NON-STRUCTURAL COEIN ~ coagulopathy ~ ovulatory dysfunction ~ endometrial (disorders of endometrium) ~ iatrogenic ~ not yet classified >=1 may be present, so if polyps and von Willebrand P1A0L0M0-C1O0I0E0I0N0

Question 19

Approach to ovarian failure (general + tests)?

Answer 19

history physical investigations HCG, PRL, TSH endometrial biopsy (if at high risk of endo hyperplasia or malignancy) imaging: US or SIS: saline infusion sonography (ink injection into uterus) or hysteroscopy

Question 20

Explain urogenital concerns in menopause?

Answer 20

~ vaginal atrophy ~ UTIs ~ incontinence ~ pelvic prolapse estrogen receptors in vagina, bladder, urethra, pelvic floor muscles -> lack of estrogen -> atrophy of urogenital epithelium and sub epithelial tissues -> degeneration of collagen/elastin/smooth muscle + decreased blood flow to tissues -> atrophy ex. vaginal atrophy: dyspareunia, vaginal dryness, itching and irritation b/c thinning of the epithelium, less blood flow, vaginal length and diameter shrinks, nerve endings exposed, increased trauma (rugae disappears, moisture gone - thin pale dry surface) ex. more UTIs b/c mucosa thinner, decreasing levels of lactobacilli, reduced lactic acid production (ph up) ex. urinary incontinence - b/c thinning of bladder mucosa, increased irritation - > stress urinary incontinence (cough, sneeze - let go) vs urge incontinence (cannot hold), also angle of urethra and vagina changes ex. pelvic prolapse - uterus can literally prolapse (drop), sometimes out of urogenital triangle and outside

Question 21

hormone therapy for primary prevention of heart disease?

Answer 21

not recommended, b/c increased risk of breast cancer, coronary heart disease, stroke; but less hip fractures

Question 22

how does one monitor and treat bone disease in menopause (T-scores)

Answer 22

Bone mineral density scan if T score (deviation) > -1 = normal -1 to -2.5 = low bone mass (osteopenia) < -2.5 osteoporosis use FRAX tool to assess fracture probability, if high, treat, if intermediate, assess more and then decide can treat with bisphosphonates (encourage apoptosis of osteoclasts which resorb bone), raloxifine( selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis), PTH (parathyroid hormone = tripartite injection - activates osteoblasts, which builds bone), calcitonin

Question 23

Sx of hypothyroidism?

Answer 23

cold intolerance fatigue sleepiness constipation weight gain irregular + heavy cycles

Question 24

What is Sheehan’s syndrome?

Answer 24

postpartum pituitary necrosis due to severe post partum hemorrhage

Question 25

Sx of Turner's syndrome?

Answer 25

primary amenorrhea short stature other congenital abnormalities

Question 26

Why worry about uncontrolled diabetes in pregnancy? Tx for diabetes in pregnancy?

Answer 26

uncontrolled diabetes is teratogenic - fetal anomalies, stillbirths, macrosomia, neonatal hypoglycemia. during pregnancy -\> diet and exercise, insulin if levels still high. glyburide or metformin controversial.

Question 27

Tx for abnormal bleeding (ex. 3 weeks) after medroxyprogesterone?

Answer 27

1. r/o pregnancy - #1 cause of AUB 2. oppose progesterone with estrogen.

Question 28

Parvovirus B19 poses what risks to newborn?

Answer 28

readily crosses placenta: high rate of spontaneous abortion if early in pregnancy, later in pregnancy destroys immature RBCs, causing anemia and lead to hydrops. unpredictable - most women with prenatal infection deliver healthy infants.

Question 29

acute pyelonephritis vs cystitis in pregnant women?

Answer 29

acute pyelonephritis: fever, nausea, vomiting, chills. flank pain on exam. labs: urinalysis and urine culture. results: pyuria, + leukocyte esterase, microscopic hematuria. if WBCs present in urine - \> renal pyuria -\> pyelonephritis. uncomplicated cystitis: gross hematuria. shoot preggos with IV antibiotics

Question 30

Sx of mastitis?

Answer 30

localized inflammation breast pain localized erythema fever, myalgias most common during first 6 weeks postpartum. culture breast milk if possible for right antibiotic cocktail. Staph aureus, especially MRSA is the most common organism for mastitis, or mastitis + abscess. blood cultures useless unless septic.

Question 31

How do you Tx infants born of HepB+ mom?

Answer 31

1. immune globulin 2. Hep B vaccine - entire series, then test for seroconversion.

Question 32

When to give influenza vaccine to preggo patient?

Answer 32

any time during gestation, inactivated only (IM, not live nasal). studies show protective effect for infant up to age of 6 months. can immunize family members if immunocompromised.

Question 33

Best tx for dysmenorrhea in a teen?

Answer 33

likely due to endogenous prostaglandins. OCPs have been used, but not as effective as prostaglandin synthase inhibitors.

Question 34

What is endometriosis? What are some common locations for it?

Answer 34

non-cancerous disorder where uterine (specifically endometrial tissue) travels and implants in other organs. Most often ovaries (most common), broad ligaments, posterior cul-de-sac, uterosacral ligament

Question 35

Presentation of endometriosis? Diagnosis?

Answer 35

Presentation: pelvic pain, abnormal uterine bleeding, infertility, dyspareunia and midline pelvic pain around time of menses, classically after several years of pain-free menses. Some women asymptomatic - level of disease not parallel with amount of symptoms. diagnose via biopsy via pelvic laparoscopy.

Question 36

small (

Answer 36

keys: young, cyst small ( 5 cm + symptomatic -\> laparoscopy always order CA-125 (cancer antigen 125) in post-menopausal patient.

Question 37

What are obstetrical cases with high chance of DIC?

Answer 37

abruptio placentae (most common) saline-induced therapeutic abortion retained dead fetus or products of conception amniotic fluid embolism =\> placental tissue with tissue factor activity exposed to maternal circulation also infection, esp. with gram -ve organisms. -ve endotoxins cause generation of tissue factor.

Question 38

What are reasons for symmetric and assymmetric IUGR?

Answer 38

symmetric intra-uterine growth retardation: inadequate growth of head, body and extremities (decreased rate of cell reproduction). Usually prior to 32 weeks and has 25% of chromosomal abnormalities (tri 13, 18, 21). Assymmetrical IUGR usually occurs in early third trimester - fetus is undernourished. Here, head is normal, but abdomen is small, b/c energy is spent growing key organs like brain and heart, at the expense of the liver (no extra calories to store glycogen for birth), muscle, and ado fat. usually due to placental insufficiency.

Question 39

What is amniotic fluid embolism?

Answer 39

Amniotic fluid embolism (AFE) - rare obstetric emergency in which amniotic fluid, fetal cells, hair, or other debris enters the mother's blood stream via the placental bed of the uterus and trigger an allergic reaction.

Question 40

Sx of amniotic fluid embolism?

Answer 40

allergy: SOB hypoxia, sudden hypotension tachy, DIC, altered mental status, seizures, coma. Usually during labour, C/S or 30 mins post. 50% associated with oxytocin stimulation.

Question 41

46 yo presents with lower abdominal/pelvic pain. On exam, with the patient in a supine position, you palpate the tender area in her abdomen. When you have her raise both legs off the table while you palpate the abdomen, her pain intensifies. Which is the most likely diagnosis: appendicitis, hematoma w/i abdominal wall musculature, diverticulitis, PID, ovarian cyst?

Answer 41

A: Carnett’s sign is the easing of the pain of abdominal palpation with tightening of the abdominal muscles (both legs raised). If the cause is visceral, flexed abdominal muscles would guard the source of pain from examining hand. In contrast, if pain intensifies during Carnett’s -\> source of pain is in the abdominal wall itself, and abdominal hematoma is likely.

Question 42

28 GA with recent onset of itching, no rash. Pruritus started on palms and soles, then spread to rest of body. labs indicate elevated serum bile acids, mildly elevated bilirubin and liver enzymes. Dx?

Answer 42

gestational intrahepatic cholestasis (something to do with progesterone affecting motility). Ursodeoxycholic acid was shown to control pruritus and decreased liver function, safe for mom and kids.

Question 43

Primary amenorrhea, ambiguous genitalia, no uterus, secondary sexual characteristics. Ddx?

Answer 43

Approach: ddx if male karyotype, ddx if female karyotype if male: external genitalia needs androgens for development: androgen insensitivity: high testosterone/DHT; karyotype 46 XY 5 alpha reductase deficiency - testosterone not converted to DHT (more potent androgen) -\> depending on level, external female, ambiguous or male. If female, primary amenorrhea, remove testicles internally due to higher rates of testicular cancer. if female: Mullein agenesis -\> internal structures simply did not develop: low testosterone/DHT; karyotype 46 XX

Question 44

Ambiguous genitalia + abnormal BP + weird Na+/K+ balance (hypotension, hyperkalemia, hyponatremia).Ddx?

Answer 44

congenital adrenal hyperplasia of 21-OH deficiency -\> testosterone made, but not cortisol or aldosterone -\> water not retained, Na+ out and K+ in (pump) -\> hypotension, virilization, hyperkalemia, hyponatremia. Test 17 OH progesterone

Question 45

TTx for genital warts in pregnancy?

Answer 45

Tricholoroacetic acid on vaginal mucosa, both in pregnancy and non-pregnancy. Memory aid, vagina has different colours, and warts add even more: tricholoro+ acetic (need acid)]

Question 46

Types of urinary incontinence? And pathophys of each?

Answer 46

**Stress incontinence** - "loss of urine with increased intra-abdo P" = inability to properly oppose abdominal pressure (urine will only stay in if urinary structures can oppose abdominal pressure with equal force) - urine leaks with laughing, exercise, etc. "very top and very bottom" - very top - abdominal pressure - very bottom - urethra and urethral spincter are weak - cannot maintain pressure when intraabdominal P is high - \> urine leaks **Overflow incontince** - frequent dribbling +/- urgency, inability to fully empty bladder no urge to empty until bladder really full, inability to empty fully - due to underreactive bladder (ex. neuropathy) or urethal obstruction **Urge incontience** - wanting to go to the bathroom even if very little in the bladder - feeling of urgency and immediate emptying of bladder - due to overactive bladder Mixed Congenital Fistula **Neuro:** bladder - parasympathetic S1,2,3 - cholinergic muscarinic internal sphincter - sympathetic external sphincter - pudendal nerve - somatic

Question 47

What to look for on Hx and PEx for urinary incontinence?

Answer 47

**Hx: think increased abdo pressure, CV, neural, GI, etc** **#1 reversible causes; DIAPPeRRS** delirium infection atrophic vaginitis - think about lichen sclerosus and labial fusion, etc pharmacological - ex. loop meds psychiatric renal issues reduced mobility stool impaction **Neuro:** DM, neuro like MS - bladder issues could indicate progression **Mechanics**: leakage with sneezing/laughter; is there an urge to empty (bladder or neural), up at night (stress incontinence would not be up at night) Prev. med Hx: CV - CHF -\> edema -\> increased abdo pressure COPD -\> increased abdo pressure don't forget about obstetrics too! prior pelvic surgery, obstatrical issues, radiation **Exam:** "general physical to r/o life threatening disease" again: CV, Lungs, GI, neuro, GU, so functional status: demented/mobile/morbidly obese - different management neuro status - internal urethral spincter= sympathetic control, muscle atrophy (neural) CV - CHF edema, etc COPD, etc - increased pressure masses! signs of infection! pelvic exam: signs of prolapse: cystocele, rectocele, enterocele, etc, signs of atrophic changes rectal exam: bowel inpaction, etc do full bladder/empty bladder comparison

Question 48

Labs and treatment for urinary incontinence?

Answer 48

**Labs: think about your differential: infection, cancer, renal, pressure issue (can't really test neuro and GI)** infection: urinalysis and culture, can do CBC just for fun cancer: cytology (urine cytology can have some cancerous cells from bladder) Pearl: if pyelonephritis, would have a lot of WBC in urine b/c of circulation in kidney, but only trace of hematuria, if bladder, low WBC b/c not well vascularized, but gross hematuria b/c close to exit ) kidneys: renal function studies = GFR, Cr, etc urodynamics (for pressure issues) - cystometry (all about bladder: measure of residual volume, volume at which urge happens, bladder flow rate, capacity,....), cystoscopy, etc. Expensive, so only if potential surgical, to r/o obstruction or to confirm that detrusor is off **Treatment:** conservative: Kegels, avoid diuretics like coffe medical: estrogen therapy in some conditions, alpha adrenergic agonists for stress incontinence (ex. pseudoephedrine) surgical: surgical sling under urethra to help it deal with abdo pressure, mesh slings in obturator etc

Question 49

What do you know about pelvic prolapse, including exam, diagnosis, treatment?

Answer 49

Pelvic Prolapse - not discussed in class, but on learning objectives cystocele = bladder cystourethrocele uterocele vaginal prolapse rectocele enterocele (intestine) Grading: just like birth, ischial spines I at or above ischial spines II btwn ischial spines and introitus III up to introitus IV past introitus Risks: increased abdominal pressure: obesity, COPD, fibrosis, heavy exercise postpartum, parity tumour/mass genetc estrogen loss of aging postsurgical loss of innvervation: paralysis, MS S/S: pressure, organ protrusion, INCONTINENCE, dyspareunia, spotting, groin pain Dx via visualization: MUST BE EXAMINED IN SUPINE AND STANDING Tx: asymptomatic - regular follow up, Kegels, maybe some estrogen symptomatic - pessary or surgical treatment Complications: urinary retention, constipation, UTIs, ulcers, vaginal bleeding