2 - Physiology Flashcards
What do LH and FSH do in women?
Hypothalamus releases gonadotrophin-releasing hormone (GnRH) to stimulate anterior pituitary to produce LH and FSH
LH and FSH stimulate development of follicles in the ovaries.
Theca granulosa cells around the follicles secrete oestrogen.
Oestrogen has negative feedback effect on the hypothalamus and anterior pituitary to suppress the release of GnRH, LH and FSH.
What is the role of oestrogen and progesterone?
Oestrogen
Produced by ovaries in response to LH and FSH. Promotes female secondary sexual characteristics:
- Breast tissue development
- Growth and development of the female sex organs (vulva, vagina and uterus) at puberty
- Blood vessel development in the uterus
- Development of the endometrium
Progesterone
Produced by the corpus luteum after ovulation. Produced mainly by the placenta from 10 weeks gestation onwards.
Acts on tissues that have previously been stimulated by oestrogen. Progesterone acts to:
- Thicken and maintain the endometrium
- Thicken the cervical mucus
- Increase the body temperature
What are the stages of puberty in girls?
AGED 8-14
- Breast buds (Thelarche)
- Pubic Hair
- Axillary hair and thicker pubic hair
- Menarche
FSH levels plateau about a year before menarche. LH levels continue to rise, and spike just before they induce menarche.
Why do overweight children go through puberty earlier?
Adipose tissue contains aromatase that converts androgens to oestrogens
What are the different phases of the menstrual cycle?
Follicular phase: from start of menstruation to the moment of ovulation (the first 14 or so days in a 28-day cycle)
Luteal phase: from moment of ovulation to the start of menstruation (strictly 14 days)
What happens in the follicular phase of the menstrual cycle?
FSH stimulates further development of secondary follicles. As the follicles grow, the granulosa cells that surround them secrete increasing amounts of oestradiol (oestrogen).
Oestrogen has negative feedback effect on the pituitary gland, reducing the quantity of LH and FSH produced.
Rising oestrogen also causes the cervical mucus to become more permeable, allowing sperm to penetrate the cervix around the time of ovulation
One of the follicles is the dominant follicle.
Luteinising hormone (LH) spikes just before ovulation, causing the dominant follicle to release the ovum from the ovary
What happens in the luteal phase of the menstrual cycle?
NB - Image
Follicle that released the ovum collapses and becomes the corpus luteum
Corpus luteum secretes high levels of progesterone, which maintains the endometrial lining and thickens cervical mucus
If fertilisation syncytiotrophoblast releases HCG to maintain the corpus luteum. Without hCG, the corpus luteum degenerates.
This fall in oestrogen and progesterone causes the endometrium to break down and menstruation to occur. Stromal cells of the endometrium release prostaglandins.
Negative feedback from oestrogen and progesterone on the hypothalamus and pituitary gland ceases, allowing FSH and LH to his again
What are the different stages a fertilised egg goes through before implantation?
- Zygote
- Morula
- Blastocyst (Syncitiotrophoblasts)
What is HCG produced by and why is it important?
Syncitiotrophoblasts after implantation
Maintains corpus luteum to allow it to keep producing progesterone and oestrogen until the placenta can take over
After implantation what is the next stage the blastocyst undergoes?
Cells of embryo blast split in two, with the yolk sac on one side and the amniotic cavity on the other. The embryonic disc sits between the two
Chorion surrounds this complex (cytotrophoblast and the syncytiotrophoblast)
How does the placenta develop?
Syncytiotrophoblast grows into endometrium and forms finger-like projections called chorionic villi, containing fetal blood vessels.
Chorionic villi nearest connecting stalk (chorion frondosum) are the most vascular and contain mesoderm. Cell proliferate and become the placenta. The connecting stalk becomes the umbilical cord.
Placental development is usually complete by 10 weeks gestation.
What are lacunae and how do they form?
Space around the chorionic villi that fills with maternal blood
Trophoblast invasion of the endometrium sends signals to the spiral arteries reducing their vascular resistance and making them more fragile. The blood flow to these arteries increases, and eventually they break down, leaving pools of blood called lacunae Maternal blood flows from the uterine arteries, into these lacunae, and back out through the uterine veins
What is the importance of the lacunae if they do not form properly?
If formation of these are inadequate can lead to pre-eclampsia
When there is high vascular resistance in the spiral arteries causing a sharp rise in maternal blood pressure
What are some of the functions of the placenta in general terms?
- Respiration
- Nutrition
- Endocrine
- Excretion/Kidneys (urea and creatinine)
- Immunity
How does oxygen get from mother to baby?
Fetal haemoglobin has higher affinity for oxygen so when the vessels run next to each other in the chorionic villi the oxygen is pulled from the mother’s blood
Carbon dioxide, hydrogen ions, bicarbonate and lactic acid are also exchanged in the placenta, allowing the fetus to maintain a healthy acid-base balance.
What is the endocrine function of the placenta?
HCG: maintain corpus luteum until can make it’s own progesterone
Oestrogen: softens tissues and makes them more flexible for birth, enlarges breasts and nipples
Progesterone: Week 5, maintains pregnancy by relaxation of the uterine muscles (preventing contraction and labour) and maintains the endometrium.
What are some of the side effects of raised progesterone in pregnancy?
All due to the relaxation of muscles it causes
- Heartburn
- Constipation
- Hypotension, headaches and skin flushing (relaxing of blood vessels)
- Raised body temperature
What are some changes to the following systems in pregnancy:
- Skin
- Endocrine
- Respiratory
What are some changes to the following systems in pregnancy:
- Renal
- Cardiovascular
- Blood
What are some changes to the following systems in pregnancy:
- Myometrium
- Cervix and Uterus
- Uterus
- Vagina
What are the three stages of labour?
1st Stage: From onset of true regular contractions until 10cm cervical dilatation
2nd Stage: From 10cm to delivery of baby
3rd Stage: From delivery of baby to delivery of placenta
What hormone controls labour?
Prostaglandins
Ripe cervix before delivery and then stimulate contraction of uterus
Prostaglandin E2 (Dinoprostone) can be given as a pessary to induce labour
What happens during the first stage of labour?
Cervical dilation and effacement occurs and a show (mucus plug) will come out. Baby head into pelvis
Usually takes 8 hours if first labour or 5 hours for subsequent
Latent Phase: 0 to 3cm dilation of the cervix, irregular contractions
Active Phase: 3-7cm dilation, regular contractions
Transition: 7-10cm, strong regular contractions
What observations need to be done for a woman in the first stage of labour?
Use a partogram
- Heart rate hourly
- Vitals 4 hourly
- Urinary frequency
- Frequency of contractions half hourly
- Vaginal exam hourly
- Regular analgesia
What happens during the second stage of labour?
From fully dilated to deliver and depends on 3 Ps (power, passenger, passage)
- Power: strength of contractions
- Passenger: Size, Attitude, Lie, Presentation
- Passage: shape and size
What are the different types of breech presentation?
Feet closest to cervix
- Complete (hips and knees flexed like cannonball)
- Frank (hips flexed and knees extended so bottom first
- Footling (foot through cervix)
What are the seven cardinal movements of labour?
- Engagement
- Descent
- Flexion
- Internal rotation
- Extension
- Restitution and External rotation
- Expulsion
How is the descent of the baby recorded?
Relative to mother’s ischial spines in cm
-5cm: When head is up around pelvic inlet
0cm: Head at ischial spines ENGAGED
5cm: Head descended further out
What extra observation needs to be done in the second stage of labour?
Vaginal exam is done 4 hourly not 1 hourly
Do intermittent auscultation of foetal heart rate after a contraction for 1 minute at least every 5 minutes
Palpate woman’s pulse every 15 minutes
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How long is the second stage of labour?
Nulliparous: <3 hours
Multiparous: <2 hours
If prolonged then instrumental assistance! C-section has high maternal morbidity
What are the different management options for the third stage of labour?
Active
- Use of uterotonic drug (IM Oxytocin) to encourage expulsion of placenta and membranes
- Deferred cutting and clamping of cord
- Controlled traction of cord once signs of separation
Physiological
- Drugs not used
- Cord not clamped until pulsation stopped
- Placenta delivered by maternal effort
How long is the third stage of labour?
Active: 30 minutes
Physiological: 60 minutes
If delay then transfer to obstetric unit, be wary of PPH
What is the side effect of oxytocin for third stage of labour?
Nausea and vomiting
What are some signs of placenta separation and what are some risks associated with cord traction?
- Gush of blood
- Lengthening of the umbilical cord
- Ascension of the uterus in the abdomen
Risk of inverting uterus and risk of PPH if not done carefully
What is
- Premature Menopause
- Perimenopause
- Postmenopause
Natural cessation of menstruation due to loss of ovarian follicular activity, ages 45-55
Premature: Before the age of 40
Perimenopause: Irregular menstrual cycle and vasomotor symptoms
Postmenopause: Time after periods have ceased for 12 months
What is the physiology of menopause?
Supply of oocytes fall so reduction in follicular activity
Less oestrogen and inhibin being produced so less negative feedback on pituitary so increased LH and FSH
Decline in oestrogen also causes vasomotor symptoms and eventual amenorrhea as endometrium not thickening
Oestrogen: Low
LH and FSH: raised
What are some perimenopausal symptoms?
Symptoms due to a lack of oestrogen. Last for around 7 years
- Irregular periods
- Hot flushes
- Night sweats
- Emotional lability
- PMS
- Joint pains
- Vaginal dryness
- Heavier or lighter periods
- Reduced libido
What are some of the risks associated with low oestrogen in the menopause?
- Cardiovascular disease and stroke
- Osteoporosis
- Pelvic organ prolapse
- Urinary incontinence
How is the diagnosis of menopause made?
If >45 can be made by clinical features, no bloods needed but can do FSH test
- Perimenopause: vasomotor symptoms and irregular periods
- Menopause: no period for at least 12 months and not using hormonal contraception OR symptoms in women without a uterus
When can women stop taking contraception when they are menopausal?
- Two years after LMP if <50
- One year after LMP if >50
Can only use depot if <45 as risk of reduced BMD
How can the symptoms of menopause be managed?
Lifestyle Modifications: e.g sleep in cool room, wear lighter clothing
Vasomotor: HRT (1st line) or Clonidine or CBT. Black Cohosh has some evidence but safety unknown
Urogenital Atrophy: Vaginal oestrogen and vaginal moisturisers if doesn’t help use HRT
Depression: SSRIs like Duloxetine and Citalopram, CBT. If just low mood then offer HRT and CBT.
Contraception: needed for 1-2 years
Low libido: HRT and then testosterone supplement if HRT not working
When should you not use a FSH test to diagnose menopause?
- Over 45
- If using hormonal contraception
When would you use cyclical progesterone and continuous progesterone in HRT?
Cyclical progesterone: 10 – 14 days per month for women that have had a period within the past 12 months. Cycling the progesterone allows patients to have a monthly breakthrough bleed during the oestrogen-only part of the cycle
Continuous progesterone is used when the woman has not had a period in the past:
- 24 months if under 50 years
- 12 months if over 50 years
HRT is given to help alleviate menopausal symptoms caused by a decline in oestrogen. What are the different HRT regimes and what are the indications for each?
NB - Image
Think of the three questions:
Women without uterus: Oestrogen Only HRT
Women with uterus: Combined Oestrogen and Progesterone HRT, to prevent endometrial hyperplasia and cancer
Women still having periods: Cyclical HRT with breakthrough bleeds
Women not had period for 12 months or more: Continuous HRT
What is clonidine used for and what are some of the side effects of this?
Can be used for hot flushes in menopause when contraindications for HRT
Agonist of alpha-2 adrenergic receptors and imidazoline receptors so lowers heart rate and BP
SE: dry mouth, headaches, dizziness, fatigue, if sudden withdrawal then rapid rise in BP and agitation
What are some alternative therapies that are often used to help with vasomotor symptoms in menopause?
Safety and efficacy are unclear and they can interact with other medications
- Black cohosh: may cause liver damage
- Dong quai: may cause bleeding disorders
- Red clover: oestrogenic effects
- Evening primrose oil: significant drug interactions, clotting disorders and seizures
- Ginseng: mood and sleep benefits
What are the indications for HRT?
- Replace hormones in premature ovarian insufficiency, even without symptoms
- Reducing vasomotor symptoms such as hot flushes and night sweats
- Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
- Reducing risk of osteoporosis in women under 60 years
What are the benefits of HRT?
- Improved vasomotor and other symptoms of menopause (including mood, urogenital and joint symptoms)
- Improved quality of life
- Reduced the risk of osteoporosis and fractures
What are the risks of HRT?
Risks higher in older women and prolonged use:
- Breast cancer (only combined HRT)
- Endometrial cancer
- VTE
- Risk of stroke and coronary artery disease (not with oestrogen only HRT though)
How can we reduce the risks of HRT?
- If women has uterus add progesterone to protect against endometrial cancer
- Use patches over pills if high risk VTE or if BMI>30
What are some contraindications for HRT?
- Undiagnosed abnormal bleeding
- Endometrial hyperplasia or cancer
- Breast cancer
- Uncontrolled hypertension
- VTE
- Liver disease
- Active angina or myocardial infarction
- Pregnancy
What investigations do you need to do before starting a woman on HRT?
- Check no contraindications
- Take a family history for oestrogen dependent cancers (e.g. breast cancer) and VTE
- Check BMI and blood pressure
- Ensure cervical and breast screening is up to date
- Encourage lifestyle changes that are likely to improve symptoms and reduce risks
When would you use oral oestrogen in HRT over transdermal (patches and gels)?
- Poor compliance with oral
- High risk of VTE
- CVD
- Headaches
Why is cyclical progesterone used before the cessation of periods in the menopause?
If used continuous leads to irregular breakthrough bleeding which would lead to lots of unnecessary investigations for abnormal bleeding
Continuous has better endometrial protection so switch to this after a year of cyclical if >50 or two years if <50. Do the switch during the breakthrough bleed
What are the different ways that progesterone can be administered in combined HRT?
- Oral
- Transdermal Patches
- Mirena IUS (licences for 4 years and has added benefit of contraception)
What are the different types of progestogens used in combined HRT?
If woman experiences side effects with one class then switch to another
C19 progestogens: derived from testosterone, and are more “male” in their effects. Examples are norethisterone, levonorgestrel and desogestrel. These may be helpful for women with reduced libido.
C21 progestogens: derived from progesterone, and are more “female” in their effects. Examples are progesterone, dydrogesterone and medroxyprogesterone. May be helpful for women with side effects such as depressed mood or acne
What is the ‘best’ HRT regime?
Oestrogen Patches: lower risk of VTE
Mirena IUS: contraceptive, lighter bleeding, no prostogenic side effects
What advice should you give a woman starting HRT?
- Side effects often settle with time, so it is worth persisting for at least three months with each regime
- It takes 3 – 6 months of treatment to gain the full effects
- Problematic or irregular bleeding is an indication for referral to a specialist
- Ensure the woman has appropriate contraception
- Stop oestrogen-containing contraceptives or HRT 4 weeks before major surgery
What are some side effects of HRT?
Oestrogenic:
- Nausea and bloating
- Breast swelling
- Breast tenderness
- Headaches
- Leg cramps
Progestogenic:
- Mood swings
- Bloating
- Fluid retention
- Weight gain
- Acne and greasy skin
Unscheduled bleeding can occur in the first 3 – 6 months of HRT, if continues after this refer 2 week wait for endometrial cancer
How do you stop HRT?
Either gradually reduce or suddenly stop
Gradually reducing HRT may limit symptoms in the short term
If a woman has cardiovascular risk factors can they still have HRT?
Yes if they are optimally managed
Does not increase cardiovascular disease risk when started under 60 and does not increased the risk of dying by CVD
If oestrogen only does not increase the risk of CVD
What is premenstrual syndrome?
Psychological, emotional and physical symptoms that occur during the luteal phase of the menstrual cycle
The symptoms of PMS resolve once menstruation begins. Symptoms are not present before menarche, during pregnancy or after menopause
When severe and have a significant effect on QoL this is called premenstrual dysphoric disorder
What is the cause of pre-menstrual syndrome?
Fluctuation in oestrogen and progesterone
Increased sensitivity to progesterone in the luteal phase
What are some presentations of PMS?
- Low mood
- Anxiety
- Mood swings
- Irritability
- Bloating
- Fatigue
- Headaches
- Breast pain
- Reduced confidence
- Cognitive impairment
- Clumsiness
- Reduced libido
Can also occur in response to cyclical HRT and COCP due to the progesterone
How is PMS diagnosed?
Symptom diary over two cycles.
Will show cyclical symptoms that occur just before, and resolve after, the onset of menstruation.
Definitive diagnosis using GnRH analogues to halt the menstrual cycle and temporarily induce menopause, to see if the symptoms resolve
How is PMS managed?
- General healthy lifestyle changes, such as improving diet, exercise, alcohol, smoking, stress and sleep
- COCP (Yasmin containing drospirenone first line, use continuously)
- SSRI antidepressants
- CBT
What medication can be used for PMS breast pain?
Danazole and Tamoxifen
Spironolactone can be used for breast swelling and bloating
