Repro/GI Week 1
Terms
undefined, object
copy deck
- 183
- 183
- What happens with estrogen at puberty?
- Estrogens reverses from inhibitory to activating (results in GnRH pulses, then LH FSH secretion)
- Sequence of puberty in women
- Thelarche, Pubarche, Peak height velocity, menarche
- When does menarche typically occur in relation to thelarche?
- Tanner stage 4
- How long is normal menstrual cycle?
- 24-35 days
- Which part of menstrual cycle is the most variable?
- Follicular phase (normally 14 days)
- How long is the luteal phase
- Always almost exactly 14 days
- Primary vs Secondary amenorrhea
- Before or after menarche respectively
- Define primary amenorrhea
- No menses by 16 w/ normal development, no menses by 14 w/o normal development
- Define secondary amenorrhea
- No menses for 6 months
- Typical hypothalamic causes of amenorrhea
-
Athletics (Both dec GnRH and low fat)
Anorexia (low fat) - Typical pituitary causes of Amenorrhea
- Prolactinoma (via dec GnRH sec to inc Prolactin)
- Bromocriptine
- Dopamine agonist used to treat prolactinomas
- Turners
-
45 X - most common cause of prim amenorrhea.
Can be 46 XX w/ defective X (and can give sec amenorrhea)
Has high gonadotropins - POF Gene
- Premature Ovarian failure gene (hypothesized)
- Uterine/Outflow causes of amenorrhea
- Vaginal septum, imperforate hymen
- Imperforate hymen
-
Hymen doesn't canalize.
Presents with primary amenorrhea, bulging hymen, and hematocolpos or hematometria - Vaginal septum
- Failure of canalization of vagina. NO bulge at introitus
- 184
- 184
- Where does HCG come from?
- Syncytiotrophoblast
- What does HCG do?
- Prevents involution of corpus luteum so the CL can continue to make estrogen/progesterone until placenta takes over (8-12 wks)
-
Estrogen effects in pregnancy
(on breast, skin, kidney) -
Breast - Duct growth
Skin - Chloasma, Palmar erythema
Renal - Increased sodium loss - Progesterone effects in pregnancy (breast, vascular, kindey, GI, Uterus)
-
Breast - Alveolar hypertrophy
Vascular - Smooth muscle relaxation (dec PVR)
Renal - Increased reabsorption
GI - Dec motility
Uterus - hypertrophy - How does pregnancy affect maternal glucose conc?
- Increased standard dev (Higher when fed, lower when fasting)
- HPL
- Human placental lactogen - Increases insulin level, but decreases sensitivity in peripheral tissue
- How do pregnancy hormones (Est, Prog, HPL) affect insulin
- Increase
- How does pregnancy affect blood pressure
- Decreases PVR, so BP decreases (only during 2nd trimester)
- 3 components of the cervix
- Smooth Muscle, Collagen, Fibrous CT
- What happens to the cervix prior to labor?
-
Collagen breakdown
increased fibrous & glycoprotein ground substance - Bishop Score
- Measurements of the cervix indicating it's readiness for labor
- Puerperium
- After pregnancy - Hypercoagulable, return of ovulation, weight loss
- 185
- 185
- Stages in blastocyst development
- 2, 4, 8, morula, early blast, late blast
- Decidua basalis
- uterus directly underneath chorion
- Decidua capsularis
- Outside of amnionic sack w/o contact with uterus
- Decidua vera
- Uterus away from amnionic sack
- Explain circulation in placenta
- Works like the lung⬦ Arteries from fetus carry deox blood into placenta, veins carry oxygenated blood out.
- What are the layers of the placenta
- Amnion, chorion, decidua (basalis or parietalis)
- Three functions of placenta
- 1. Steroid, peptide hormone synthesis 2. Transport 3. Respiratory gas exchange
- Functions of Progesterone, 16-OH, 17-OH
-
MARSH
1. Mammary devel
2. Adrenal (fetal) hormone substrate
3. Relax smooth muscle
4. Slow GI motility
5. Hyperventilate - 5 Functions of Estrogen (E1, E2, E3)
-
PUBLiC
Progesterone receptors (inc)
Uterine blood flow (inc)
Blood vol (inc)
Lactation (inhibit)
Carb metab. change - Explain HcG throughout pregnancy
- Peaks at about 8 weeks, and then declines as placental hormones take over
- What are the two barriers to diffusion in the placenta
- 1. Syncytiotrophoblast 2. Fetal capillary endothilia
- What two things are specifically transported by receptor mediated endo in the placenta
- IgG, LDL
- What two things are specifically not transported across the placenta?
- Protein, IgM
- Ductus Arteriosis
- Pulmonary artery to vena cava (to bypass lungs)
- Ductus Venosus
- From Umbilical vein to vena cava to bypass liver
- Foramen Ovale
- In heart to sort of bypass lungs
- What are two key differences in fetal circulation
- Right heart to Aorta, Left heart to head.
- Where does amniotic fluid come from
- Mostly fetal kidneys, some from fetal lung
- What thyroid related compounds can cross the placenta?
- Only Iodide and thyroid stimulating IgG's
- Hemochoral
- Means the blood leaves the mothers circulatin to enter the placenta. It’s the most permeable, but has no autoreg
- What is the expecting date of a pregnant women?
- Add 7 days and 9 months to the day of her last menses.
- 186
- 186
- Defintion of reccurrant miscarriage
- 3 or more miscarriages
- Incompetent cervix (& treatment)
-
Painless cervial dilation results in preterm birth.
Treat: Cervical cerclage - Placenta Previa
- When the placenta is covering the cervical oss. Clinically, Painless bright red bleeding in third trimester
- Marginal vs Complete placenta previa
- Marginal is off to one side
- Placenta Accreta
- Deeply invested placenta that doesn't come out properly
- Abruptio Placenta
- Premature seperation of placenta from uterine wall. Clinically - Painful uterine bleeding in 3rd trimester
- Symmetric vs Assymetric fetal growth restriction
- Asymmetric is "Head sparing"
- Causes of symmetric fetal growth restriction
- Constitutional, Cong. Infection, Cong malformation, Drugs, Chromosomal
- Causes of assymetric fetal growth restriction
- Chronic vasculopathy (hypertens, lupus, diabetes), chronic abruption, immunological, idiopathic
- Preeclampsia
- Unknown etiology. Causes hypertension, proteinuria, oliguria, thrombocytopenia, edema after 20 wks gestation (can advance to eclampsia which causes seizures)
- 187
- 187
- Gestational Trophoblastic Disease
- Any lesion that represents aberrant fertilization. From fetal tissue, marked by hCG
- Molar pregnancy - clinical
- Irregular bleeding, large uterine size, no fetal heart, high hCG
- Karyotype of Complete Molar Pregnancy
- 46 XX, all paternal
- Mechanism of complete molar pregnancy
- Fertilization of empty egg, followed by sperm duplication. Associated w/ trophoblastic neoplasia.
- Complete Molar Pregnancy - Findings
- No blood vessels, fetus or amnion, Swelling of villous stroma, Snowstorm & vesicular cysts on ultrasound, hydropic villi on histo
- Karyotype of partial molar pregnancy
- 69 XXY (2 from father)
- Invasive/Persistant GTD
- Excessive trophoblastic proliferation and local invasion. Responsive to chemo (rarely metastatic)
- Invasive/Persistant GTD - findings
- Theca Lutein Cysts, Myometrial invasion, stable or rising hCG
- Choriocarcinoma
- GTD Neoplasia. Most common after sponatneously aborted pregnancy. Sheets of anaplastic trophoblast w/o chorionic villi
- Metastasis of Choriocarcinoma
- Most commonly pelvis, vagina, lung.
- Placental Site Trophoblastic Tumor - findings
- No invasion. No chorionic villi, intermediate cytotrophoblastic cells. Often hPL or PAP
- Maternal mortality and Live Birth order
- Second is lowest, increasing after.
- What does folic acid prevent?
- Spina bifida and heart defects
- Pregnancy and stroke volume/heart rate
- Stroke volume increases early, heart rate increases late.
- Common causes of death in abortion
- Anesthesia, hemorrhage, infection, embolism
- 188
- 188 NEED SYLLABUS
- RU-486
- (Mifepristone) Progesterone competitive antagonist (although effects of inhibition may be irreversible)
- Location of action of Mifepristone
- Progesterone receptors in the decidua. Causes necrosis
- Prostaglandin & RU-486
- Greatly increases efficacy by producing uterine contractions
- Misoprostol
- A vaginal (or oral) prostaglandin used after RU486. Can induce abortion alone. Also used in gynecology to open cervix.
- Oxytocin
- Receptors in myometrium, produces labor. Dependant on cervical ripeness (add prostaglandins)
- What happens in cervical ripening?
- Collagen becomes disorganized & lengthened, Inc hyularonic acid, Increase Water, break collagen bridges
- Bishop Scores
- >8 is good - vaginal delivery is fine. < 4 unfavorable
- Prepidil
- Prostaglandin for cervical ripening near term (used w/ preterm too)
- 189
- 189 NEED SYLLABUS
- Pearl index for birth control
- Failures/100 women-yrs
- Life-table Analysis
- Failures/month use
- Decidualization
- Thinning of the uterus w/ dominant progesterone
- 19 Nortestosterone
- First generation progestin. Somewhat nonselective, so cause androgen side effects
- Drospirenone
- Spironolactone analogue w/ antimineralocorticoid & anti-androgenic activity. Contraindicated in ACE inhibitors, ang-II antagonists, K sparing diuretics, heparin, aldosterone antag, nsaid's
- Explain dose related function of estrogens
- Ovulation suppression - 20 ug. Endometrial control 30-35. Thrombotic complications >50 ug
- Progestin effects on: Carbohydrates Lipids Nitrogen Skin
-
Carb - Inc Insulin, Dec gluc tolerance
Lipids decreases cholesterol, TG, HDL, raises LDL
Nitrogen - Retention
Skin Increase sebum - Explain Contraception and MI
- Increases risk of MI in SMOKERS, actually decreases risk in non smokers
- Advantages to injectable contraception
- Lower dose --> few side effects. Very low failure rate (dis - one more day of bleeding)
- Which birth control has loswest estrogen exposure? Highest?
- Lowest - ring. Highest - patch (pill is in the middle)
- Name two implantable contraception
- Norplant and Implanon
- How does progestin work as contraception
- Slows GnRH, Suppresses LH surge, Involutes endometrium, and thickens cervical mucous
- Mechanism of emergency contraception
-
Delays ovulation
impedes tubal transport
prevents implantation - How many unprotected women will become pregnant in a given month
- 8/100
- Mirena
- Levonorgestrel-releasing IUD
- 190
- 190 NEED SYLLABUS
- Embryology of the breast
- 2 ventral bands appear in 5th-6th week (Milk Line). Milk line extends from axilla to inguinal region, and later disappears except in the pectoral area.
- Athelia
- Absence of nipple
- Polythelia
- Supernumary nipples along the milk line
- Amastia
- absence of breast (usually one)
- Anisomastia
- Significant size differences between breasts
- Symmastia
- Medial confluence of the breast
- Which hormones stimulates breast devel
- Estrogen - Ductal growth Progest & Est - Lobuloaveolar growth (also need insulin, cortisol, thyroxine, prolactin, GH)
- Montgomery glands
- Mammary sebacious glands that lubricate the nipple & secrete milk
- Coopers ligaments
- Attach skin to pectoralis fascia
- Medial blood supply to the breast
- Internal mammilary
- Lateral blood supply to the breast
- Lateral thoracic, axillary, intercostal
- Prolactin and pregnancy
- Dopamine is inhibed by estrogen resulting in more prolactin release
- What upregulates prolactin receptors
- Prolactin
- Estrogen and milk
- Estrogen required to prepare the breast for lactation, but must be removed to lactation to occur (because it interferes with prolactin binding)
- Progesterone and milk
- Decreased progesterone --> lactogenesis. Blocks induction of lactogenesis, but cannot block established lactation (b/c no receptors on lactation mammary tissue)
- Afferent arc of milk let down
- Suckling stimulates nerve roots 4&5, stimulates hypothalamic production of oxytocin & decreases hypothalamic dopamine (increasing prolactin)
- Efferent arc of milk let down
- Oxytocin to breast causes emptying of alveolar lumen
- Give 3 lactotrope activators
- PRF TRH Estrogen (cause eventual release of prolactin)
- Chlopromazine
- Along with vigorous nipple stimulation, can cause relactation
- Metoclopramide
- Relactation medicine
- 2 medications for lactation suppression
- High dose estrogen (risk of DVT), Dopamine agonists - Bromocriptine (Neither are routinely used)
- Which medication is preferred for a lactating mother
- Progestin
- Masatitis
- Usually S Aureus infection. Shooting pain in the breast. Treat w/ dicloxacillin
- Breast abcess
- Palpable mass in breast, or febrile after 2-3 days antibiotic treatment. Treat with incision, drainage, IV antibiotics
- Benign Fibrocystic breast disease
- 1/2 of women 20-50. Exaggerated response to cyclic ovarian hormones/Imbalance in estrogen/progesterone. Causes pain in the breast (usually upper out)
- Fibroadenoma
- Adolescent - 20's. Benign, but increase risk of cancer. Surgical excision if etiology unknown
- Cystosarcoma Phyllodes
- Fibroepithelial tumor. Rare, but most frequent breast sarcoma. 50's. 25%malignant, 10% metastatic. Treat = wide local excision
- Intraductal Papilloma
- Bloody nipple discharge in perimenopausal women. Usually located under areola. Tx = excisional biopsy
- Fat necrosis
- Often from blunt trauma. Ca and stellate contractions on mammogram. Tx = excisional biopsy (no inc risk of cancer)
- Duct Ectasia
- Discharge (green, grey, yellow, brown or black). Ductal inflammation, often nipple retraction
- Orange peel look on breast skin
- Carcinoma of the breast
- 191
- 191
- Which area of the breast duct is most likely to have damage/neoplasia?
- Acinar area
- 2 layers of normal breast duct lining
- One columnar on luminal side & 1 luminal (myoepithelial) layer
- Paget's disease
- Intraepidermal spread of tumor cells. Can be mammary or nonmammary
- Which mammogram picture shows the pec muscle?
- Mediolateral view
- Simple vs radical mastectomy
- Simple just removes the breast, radical is breast & axillary nodes
- 4 basic types of breast cancer
- Ducat, invasive & in situ. Lobular invasive & in situ
- Common features of invasive ductal carcinoma
- No myoepithelial layers. Invades in tubular structures.
- Common features of invasive lobular carcinoma
- 'Targetoid' appearance. Invades in single file lines.
- 4 benign breast diseases that are likely to turn into cancer
- 1. Atypical ductal epithelial hyperplasia. 2. Atypical lobular hyperplasia 3. Lobular carcinoma in situ 4. Ductal carcinoma in situ
- Types of fibrocystic changes
-
Proliferative –
Florid hyperplasia
adenosis papilloma
fibroadenoma.
Nonproliferative –
Cysts,
apocrine metaplasia,
simple hyperplasia - Benign breast disease w/ no increased cancer risk
-
CABS
Cysts,
Apocrine metaplasia,
Benign calcification,
Simple hyperplasia - Bening breast disease w/ 1.5 – 2x RR
- Florid ductal hyperplasia. Sclerosing adenosis (radial scar), Fibroadenoma, Intraductal pappiloma
- What is the most common cause of nipple discharge?
- Intraductal Papilloma
- Benign breast disease w/ 4-5x RR
- Atypical hyperplasia (ALH, ADH)
- High risk breast diseases
- LCIS DCIS
- Which class of breast cancer is worse?
- Ductal (80% of breast cnacers)
- ER+ Breast cancer
- Usually low grade ductal cancer. Bland cytological features. Forms tubules
- Basal like & Her2 + breast cancers
- High grade ductal cancers. Form sheets of cells w/ high grade nuclei
- Rank the 3 main groups of breast cancer (receptor groups)
- ER+ is best, Her2 is middle, Basal like is worst.
- What is the most important prognostic indicator in breast cancer
- Lymph node status
- What 4 things are ER+ patients associated with
- 1. Older age. 2. Better prognosis. 3. Lower grade. 4 Her2 negativity
- Tamoxifen
- ER antagonist for breast cancer treatment.
- What 4 things are Her2+ patients associated with
- 1. Young 2. High grade 3. Poor prognosis 4. ER negativitiy
- Herceptin
- Monoclonal antibody used to treat Her2+ patients
- Her 2
- Oncogene on chrom 17