Week 4 Flashcards

Question

Progestogen only pill

Answer 1

Synthetic progesterone -desogestrel/levonorgestrel/norethisterone/drospirenone Should be taken daily at the same time each day, every day No pill free interval Mode of action: -prevent ovulation -thicken cervical mucus -thin endometrium Failure rates: -perfect use 1% failure -typical use 9% failure Be aware- traditional vs desogestrel POPs

Answer 2

Benefits: -effective, reversible -now available OTC Disadvantages: -menstrual irregularities -same time each day- 12 hour window for desogestrel (3 hours traditional POPs) -functional ovarian cysts -hormonal (headaches, changes to mood, depression, bloating, breast tenderness)

Answer 3

Much fewer contraindications than combined methods No increased stroke risk See UKMEC for full list -current breast cancer -severe liver disease/liver tumours -stroke/IHD

Answer 4

External condom: -latex/latex free, placed over an erect penis before any contact -acts as barrier to stop sperm entering the vagina -Perfect use 2% failure, typical 17% -single use only, check date, kite mark, not damaged, avoid -oil based lubricants, STI and HIV protection Internal condom: -inserted before sex, loosely lines vagina/rectum, partially covers vulva, acts as barrier to sperm -perfect use 5% fail, typical use 21% -single use only, STI and HIV protected

Answer 5

Reusable flexible latex or silicone device Put into vagina to cover cervix Acts as barrier to sperm Used with spermicide Can be inserted up to 3 hours before sex Needs to be left in for 6 hours after sex Perfect use 4-8% failure Typical use 12-29% failure Do not offer STI or HIV protection

Answer 6

2 categories: -fertility awareness methods FAM -lactational amenorrhoea

Answer 7

Identify a fertile window and avoid UPSI around this time The main fertility indicators are which should be recorded daily: -basal body temperature -cervical secretions (cervical mucus) -the length of your menstrual cycle Failure rate between 1-25% Apps available

Answer 8

Advantages: -can be used to avoid pregnancy or plan for one -no physical side effects -in couples control/may improve communication -avoids hormones/devices -acceptable to all faiths/cultures Disadvantages: -there are much more reliable methods -need to have regular cycles -takes 3-6 menstrual cycles to learn effectively -traditionally time consuming, requires high motivation -illness, lifetsyle, stress or travel may make fertility indicators harder to interpret -need to avoid sex or use condoms during fertile time -no STI protection

Answer 9

For post partum women -baby <6m old -woman must be amenorrhoeic -exclusively breast feeding- 4hrly in day, 6hrly at night If all 3 criteria are met: -typical failure rate -2% -perfect use failure rate -0.5%

Answer 10

Male- vasectomy -cutting /tying vas deferens Failure rate 1 in 2000 Permanent and irreversible on NHS Doesn’t affect sex drive or erections Ejaculation occurs but no longer contains sperm Use contraception for 8-12 weeks after until semen analysis

Answer 11

Works by tubal occlusion- preventing egg and sperm meeting -filshie clips -salpingectomy Failure rate 1 in 200 Permanent and irreversible on NHS Age/parity is not a restriction

Answer 12

To be given after sex 2 categories: copper IUD- gold standard, oral methods: ulipristal acetate (ellaOne), levonorgestrel (levonelle) Copper IUD: -can be inserted up to 120 hours after first UPSI -or within 5 days of the earliest expected ovulation -overall efficacy 99.9%, benefits and risks as for non emergency copper IUD -can be used for ongoing contraception or removed once pregnancy excluded

Answer 13

Ulipristal acetate: -current brand ellaOne single 30mg tablet, licensed for up to 120 hours after sex -synthetic progesterone receptor modulator -primary mode of action- delays ovulation Prevents about 60-80% of expected pregnancies Effectiveness decreased by progestogen contraception used 7 days before or 5 days after Can be used multiple times per cycle Levonorgestrel: -single tablet- 1.5mg levonorgestrel (3mg if BMI>26) -efficacy up to 96 hours -high dose progesterone- delays ovulation -use >72 hours outside the produce licence -efficacy approx 60% -can use multiple times per cycle

Answer 14

Defined as the cessation of menses for: -12 months >50 years -24 months <50 years Average age menopause in UK is 51 Early menopause <45 Premature ovarian insufficiency <40 years

Answer 15

Occur due to reduced oestrogens Hot flushes and night sweats Loss of libido Vaginal dryness Skin dryness/dry hair/thinner hair Frequency of micturition, urgency, nocturia Lethargy and fatigue Low mood/anxiety Arthralgia/myalgia Poor sleep/insomnia Palpitations

Answer 16

Increased cardiovascular risk: -MI -stroke Reduction in bone mineral density Increased total cholesterol and LDL cholesterol Decreased glucose tolerance and insulin sensitivity

Answer 17

Types HRT: -with a uterus —combined oestrogen and progestogen —-cyclical (sequential) —-continuous Without a uterus --oestrogen only

Answer 18

Transdermal: patch, gel, spray Oral LNGIUD- as progestogen component of HRT Implants Low dose vaginal oestrogen for vaginal symptoms (can be used with systemic HRT)

Answer 19

Benefits: -eases symptoms -reduces cardiovascular risk as long as started within 10 years menopause -protects bone mineral density Risks; -transdermal HRT has a safer risk profile than oral -oral preparations: DVT/PE risk, stroke and MI risk -increased risk of breast cancer 1 per 1000 per year, needs to be considered in context Risk of endometrial cancer is unopposed oestrogen is given to women with a uterus HRT is not a contraceptive

Answer 20

1st trimester

Answer 21

Mid-luteal phase: -secretory activity peaks- endometrial cells rich in glycogen and lipids ~14mm thick -glands increase in number and size -maintained by high progesterone and oestrogen levels -endometrial receptivity is marked by changes on surface epithelium

Answer 22

Pinopode formation day 16-20, reduce volume of uterus

Answer 23

Embryo attached and penetration of the endometrium and maternal circulatory system to form the placenta Embryo enters uterus bathed in the uterine secretions for 1-3 days prior to hatching from the zona pellucida “Apposition”= blastocyst loosely associates with uterine wall “Attachment”= firm adhesion “Invasion”= blastocyst attachment to the uterine wall triggers enzyme production. -degrades and invades the glycogen rich endometrial stroma -provides further nutritional support

Answer 24

Induced by progesterone Oedema, changes in ECM, vascular remodelling/angiogenesis , leukocyte infiltration (uNK cells) -uterine natural killer cells- set up environment to remodel endoemetrium, recognise embryo allowing tolerance to embryo Endometrial stromal cells undergo morphological and biochemical changes -fibroblast like-> polygonal (epithelial like) Store glycogen and lipids support blastocyst Secrete decidual proteins (characteristic markers): prolactin, IGFBP-1, tissue factor, VEGF, PIGF, LIF, IL-15 The decidua completely surrounds the implanted blastocyst by day ~10. Most is shed at parturition

Answer 25

Plakous- flat cake At term-discoid 15-25cm, 2.5-3cm thick, 500g

Answer 26

Chorionic plate: you have layer of vascularised fetal tissue (the chorion) that goes across. From there the umbilical cord arises with vessels that go off to the fetus From the maternal side: the endometrium comes around the placenta, you have lots of intervillous spaces, this is where maternal blood pools and circulates around chorionic villi Functional units of placenta- cotyledon/lobe, placental septum’s Some villi make contact with other side- anchoring villi Maternal blood transferred through whole thing from spiral arteries from endometrium to allow for exchange nutrients and gases to fetus via villi then drain back via endometrial veins

Answer 27

3 main types based on structural organisation and separation of fetal and maternal blood supplies Haemochorial- the chorion is in direct contact with the blood. Human placenta Endotheliochorial- the maternal blood vessel endothelium comes in direct contact with chorion (dog and cat) Epitheliochorial- the most primitive form- The maternal epithelium of the uterus comes into contact with the chorion (cows and pigs)

Answer 28

Trophectoderm gives rise to 3 main types of trophoblast -cytotrophoblasts (villous cytotrophoblast) -fusion of these form syncytiotrophoblasts (multinucleate very invasive) Extravillous trophoblasts EVT: interstitial, or endovascular

Answer 29

O2 and nutrients reach the developing embryo by diffusion from the surrounding decidua (histiotrophic nutrition) The initial phases of development occur at low O2 tensions

Answer 30

Lacunae form in the syncytiotrophoblast Syncytiotrophoblast invades and erodes maternal capillaries These anastomose with trophoblast lacunae to form sinusoids Intervillous space develops Start of villous development

Answer 31

Day 11-13 cytotrophoblasts invade Cytotrophoblast extend invade into syncytiotrophoblast layer form finger like projections in the decidua Primary villi cover the entire surface of blastocyst

Answer 32

Extra embryonic mesoderm (mesoblast) invades core of primary villous day 16 Mesoderm covers the entire surface of the chorionic sac Villi continue to extend into the decidua between the blood filled lacunae/sinusoids

Answer 33

Mesodermal cells differentiate to form endothelial cells and other cell types Blood vessels form an arteriocapillary network in the villi These vessels fuse with developing vessels in the stalk- to link the foetal blood system via invading vessels from the umbilical cord

Answer 34

Stem villi- basal part of villi- attached to chorionic plate Branch/intermediate villi- project from sides of stem villi Terminal villi- swellings at the tips of branch villi contain terminal vessels- form convoluted knots where the majority of exchange takes place- continue to be produced throughout gestation The cytotrophoblast layer becomes very thin but remains mostly intact 80% coverage in full term placenta

Answer 35

Essential to establish a low resistance high flow blood supply to the intervillous space Critical for normal pregnancy Spiral arteries: -resistance vessels supplying the endometrium/decidua -coiled appearance in the inner myometrium and decidua -100-150 arteries are transformed -diameter is increased 10 fold

Answer 36

First trimester: -cytotrophoblast columns form at tips of anchoring villi -Extravillous trophoblasts EVT differentiate and form interstitial and endovascular EVT EVT invade the decidua and occlude the spiral arteries Replace the endothelium and smooth muscle cells forming the endovascular trophoblast layer Establish normal utero placental dynamics Anchoring villi- cross the intervillous space- migrate deeply and attach to maternal decidua EVT plug spiral arteries- reduce blood flow to the developing placenta Creates low oxygen environment- protects fetus from oxidative stress EVT plugs breakdown initiating blood flow to intervillous space>14 weeks UNK ~70% of inflammatory cells in decidua- produce many cytokines and initiate/promote remodelling Vessels remodel outwards, lay down lots fibroid material, ECM, rigid structures. SMC undergo apoptosis or de differentiate migrate away

Answer 37

Histiotrophic phase: week 8 [O2]=20mmHg Placental perfusion- initiated week 12-14 Haemotrophic phases: week 14 [O2]=60mmHg

Answer 38

Increased maternal blood volume ~40% during first trimester Uterine blood flow increases ~20 fold during pregnancy via uterine (and ovarian) arteries Cardiac output increases by 30-40% ->25% cardiac output goes to placenta Heart rate increases 10-15bpm Increased ventilation rate

Answer 39

Umbilical arteries (deoxygenated) Fetal capillaries within villi: stem villi, intermediate, terminal Umbilical vein (oxygenated)

Answer 40

Parabiotic relationship between mother and fetus: -fetus is dependent on maternal provision of nutrition, O2, salts, organic precursors etc and removal waste products CO2, urea etc across the placenta Diffusion: O2, CO2, Na+, urea, fatty acids, sugars (facilitated), non conjugated steroids, thyroxine T4 Active transport: amino acids, iron, ca2+ Not transported: conjugated steroids most bacteria Harmful: cocaine, alcohol, caffeine, tetracycline,

Answer 41

Haemotrophic nutrition >wk 14- maternal blood delivers nutrients to fetal circulation across the placenta ~3-4cell layers separate the maternal and fetal circulations: syncytiotrophoblast, cytotrophoblasts, connective tissue, fetal capillary endothelium The intervillous spaces of a mature placenta contains ~150ml of blood exchanged 3-4x every minute

Answer 42

O2 and CO2 by passive diffusion ~40% more haemoglobin in fetal blood vs adult Fetal haemoglobin ~80% late gestation Higher affinity for O2 achieves saturation at lower pO2 -pO2 40-50mmHg ~90% Fetal Hb staurated, ~60% adult Simultaneous movement of CO2 on a concentration gradient back to the mother Double Bohr effect results in increase of ph on fetal side- promotes uptake at lower PO2

Answer 43

Uptake by insulin insensitive hexose transporters GLUT3 GLUT1 Maternal insulin regulates glucose- increases glycogen and adipose stores Maternal tissues show insulin insensitivity/resistance (due to human placental lactogen) promoting transfer of blood glucose to placenta Glucose is also metabolised to lactate which is used as an energy sourced by the fetus

Answer 44

Fetus regulates maternal amino acids metabolism through progesterone Mother retains extra amino acids and transports them to fetal circulation Some are metabolised eg serine-> glycine Fetal urea diffuses passively into the maternal blood

Answer 45

Exchange in water occurs in placenta and non placental chorion at the amnion- amniotic fluid increases from 15ml at 8 wks to 450ml at wk 20, net production decreases to 0 by wk 34 Na+ and other electrolytes transfer readily across placenta Iron: in fetal and maternal blood both free and bound to transferrin, enhanced absorption (10% 1st tri, to 30% 3rd) to cover loss to fetus, placenta, blood loss in labour Calcium: demand for fetal ossification in 3rd trimester, Ca2+ absorption is enhanced and transferred to fetal circulation Vitamins: folic acid and vit B12

Answer 46

Lipids: extracellular lipases release fatty acids from maternal lipoproteins- intracellular binding proteins FABPs transport the fatty acids in the cytosol of the syncytiotrophoblast

Answer 47

IgG transferred by pinocytosis Provide passive post natal immunity: -diphtheria -small pox -measles -chicken pox -whooping cough

Answer 48

Viruses: -CMV -rubella -coxsackie- hand foot and mouth -varicella -polio -HIV Bacteria: -spirochetes -syphilis, listeria, lymes disease Protozoa: -toxoplasma -toxoplasma gondii

Answer 49

Migration of EVTs is under tight temporal-spatial control- disturbances in this process can result in significant loss of placental function IUGR/early onset pre-eclampsia due to insufficient penetration by EVTs shallow invasions of decidua Premature loss of EVT plugs in spiral arterioles- early initiation of blood flow to placenta may lead to miscarriage

Answer 50

Leads to high pressure flow Vasoconstriction- pulsatile flow Ischaemia reperfusion injury/oxidative stress Damage to villi Failure to fully remodel maternal spiral arterioles -in PE reduced external myometrial spiral artery diameter

Answer 51

Maternal systemic syndrome caused by abnormal placentation in the first trimester- clinical symptoms present from 20 weeks onwards 3-5% pregnancies in west -severe early onset PE<32 weeks -0.5% ~30% PE cases associated with IUGR Only cure delivery placenta

Answer 52

Symptoms develop in 2nd-3rd trimester <20wks Hypertension >140/90mmHg 2 readings >4hrs apart Proteinuria >300mg/l 2+ dipstick Headache HELLP (haemolysis, elevated liver enzymes, low platelets syndrome 20% cases) Disseminated intravascular coagulopathy DIC 20% HELLP cases Seizures- eclampsia Early onset <32wks tends to be more severe

Answer 53

7-fold greater is previous PE pregnancy Maternal or paternal history PE Increased inter pregnancy interval Multiple gestation Maternal age>40 Insulin resistance, diabetes, obesity, metabolic syndrome, vascular inflammation, pre existing hypertension

Answer 54

Placenta: -abnormal trophoblast invasion -reduced differentiation and transport -altered trophoblast secretions -enhanced trophoblast apoptosis -increased fibrin deposition Maternal: systemic endothelial activation, systemic inflammatory response

Answer 55

Occurs in 8-14% of normal pregnancies- associated with pregnancy induced hypertension particularly early onset PE Blood flow to both sides placenta compromised O2 passes across by simple diffusion- reduced flow leads to fetal hypoxia Glucose transfer is generally not affected by Reduced fatty acid transfer Amino acid transport compromised -lysine, taurine, leucine, phenylalanine reduced in fetal plasma Reduced ion transport Acidosis-increased fetal lactate levels Reduced bone mineralisation in 3rd trimester

Answer 56

3-6 per 1000 Blastocyst usually implants high on posterior wall of uterus Increased risk of placental abruption/haemorrhage Marginal type II/III, complete IV, low lying I Classified as degree of coverage of cervix

Answer 57

Results from excessive trophoblast invasion Placenta invades and is inseparable from uterine wall 3 in 1000 Identified before parturition on US Can lead to vaginal bleeding in 3rd trimester Associated cases of placenta previa Associated with myometrial scarring from previous C sections Risk of maternal haemorrhage Pre term C section/hysterectomy