WOMENS HEALTH - PHYSIOLOGY Flashcards
NEWBORN SCREENING
What types of newborn screening are there?
- Newborn infant physical examination (NIPE)
- Newborn blood spot conditions
- Newborn hearing screen
NEWBORN SCREENING
When is the NIPE done?
What for?
- First within 72h of birth + Second by GP at 6–8w
- Screens for problems with hips, eyes, heart + genitalia
NEWBORN SCREENING
What is the process of the newborn blood spot conditions screen (Guthrie/heel-prick)?
- Screening on day 5–9
- Residual blood spots stored for 5 years (part of consent process) for research
NEWBORN SCREENING
What conditions does the newborn blood spot screen for?
3 genetic –
- Sickle cell disease
- Cystic fibrosis
- Congenital hypothyroidism
6 inherited metabolic –
- Phenylketonuria
- Medium-chain acyl-CoA dehydrogenase deficiency
- Maple syrup urine disease
- Isovaleric acidaemia
- Glutaric aciduria type 1
- Homocystinuria
NEWBORN SCREENING
What is the rough incidence of…
i) sickle cell disease?
ii) cystic fibrosis?
iii) congenital hypothyroidism?
iv) phenylketonuria?
v) MCADD?
vi) MSUD?
vii) IVA?
viii) GA1?
ix) homocystinuria?
i) 1 in 2000
ii) 1 in 2500
iii) 1 in 3000
iv) 1 in 10,000
v) 1 in 10,000
vi) 1 in 150,000
vii) 1 in 150,000
viii) 1 in 300,000
ix) 1 in 300,000
NEWBORN SCREENING
What specifically is tested for in…
i) cystic fibrosis?
ii) congenital hypothyroidism?
iii) phenylketonuria?
i) Immunoreactive trypsinogen
ii) TSH
iii) Phenylalanine
NEWBORN SCREENING
What is phenylketonuria?
What are the features of phenylketonuria?
What is the management?
- AR defect in phenylalanine hydroxylase (C12)
- LDs, seizures, ‘musty’ odour to urine + sweat, (fair hair, blue eyes)
- Phenylalanine restricted diet
NEWBORN SCREENING
What is the management of MCADD?
- Avoid long periods with no food
- High sugar drinks when ill
NEWBORN SCREENING
What does MSUD, IVA and GA1 have in common?
What are their differences?
What is the management?
- Issues with processing amino acids
- MSUD = leucine, isolecine + valine
- IVA1 = leucine
- GA1 = lysine, hydroxylysine + tryptophan
- Limit high protein foods
NEWBORN SCREENING
What is homocystinuria?
How does it present?
What is the management?
- Cystathionine synthetase deficiency
- Developmental delay, MSK like Marfan, fair complexion, brittle hair, dislocation of lens
- Pyridoxine (vitamin B6)
NEWBORN SCREENING
What is the newborn hearing screening?
Why is it done?
- All babies screened within 4w of birth ideally (up to 3m)
- Early identification crucial for developing speech, language + social skills
NEWBORN SCREENING
What does the newborn hearing screen involve?
What is the outcome?
- Automated otoacoustic emission (AOAE) test with some babies needing automated auditory brainstem response (AABR) test
- Refer to audiology within 4w if no clear response with one or both ears
PREGNANCY PHYSIOLOGY
What hormones increase in regards to the anterior pituitary gland?
- ACTH = rise in steroid hormones (cortisol, aldosterone) = improves autoimmune conditions (RA) but susceptible to DM + infections
- Prolactin = suppresses FSH + LH
- Melanocyte stimulating hormone = increased skin pigmentation (linea nigra + melasma = brown pigmentation)
PREGNANCY PHYSIOLOGY
What other hormones rise in pregnancy?
- T3/T4
- HCG = doubles every 48h until plateau at 8–12w then gradual fall
- Progesterone
- Oestrogen
PREGNANCY PHYSIOLOGY
What changes occur to the uterus in pregnancy?
- Increase from 100g–1.1kg
- Hyperplasia + hypertrophy of myometrium
- Decidual spiral arteries remodelled for wide bore low resistance
PREGNANCY PHYSIOLOGY
What changes occur to the cervix in pregnancy?
- Increased oestrogen = ?cervical ectropion + increased discharge
- Before delivery, prostaglandins break down collagen in cervix = dilate + efface
- Chadwick’s sign = early pooled deoxygenated blood > blue tinge
PREGNANCY PHYSIOLOGY
What changes occur to the vagina in pregnancy?
- Oestrogen > hypertrophy of vaginal muscles + increased PV discharge
- Makes bacterial + candida infection more common
PREGNANCY PHYSIOLOGY
What changes occur to the breasts?
- Increased size with increased gestation
- Fat deposition around gland tissue
PREGNANCY PHYSIOLOGY
In terms of the cardiovascular system in pregnancy, what…
i) increases?
ii) decreases?
i) Blood volume, plasma volume, CO (as increased SV + HR)
ii) Peripheral vascular resistance (can cause flushing + hot sweats) + BP in early-mid pregnancy but returns to normal by term
PREGNANCY PHYSIOLOGY
What changes can occur to the vascular system?
- Varicose veins due to peripheral vasodilation + obstruction of IVC by uterus
PREGNANCY PHYSIOLOGY
What CVS anatomical changes are there?
- Diaphragmatic elevation > heart displaced upwards/left so apex moved laterally
- Increased ventricular muscle mass + increased LV/LA size
- Altered QRS (LAD), ECG changes (inverted T waves) + flow (ES) murmurs
PREGNANCY PHYSIOLOGY
In terms of the respiratory system, what are the mechanical changes?
- Increased subcostal angle, pulmonary blood flow + tidal volume
- Decreased vital capacity + functional residual capacity
- Progesterone causes trachea-bronchial smooth muscle relaxation
PREGNANCY PHYSIOLOGY
In terms of the respiratory system, what are the biochemical changes?
- Increased oxygen consumption (20%) + RR
- Compensated resp alkalosis may occur as increased pO2 + reduced pCO2 (facilitates foetal CO2 excretion), renal HCO3- excretion to prevent this
- Increased 2,3 DPG to promote maternal Hb to release oxygen
PREGNANCY PHYSIOLOGY
In terms of the renal system, what…
i) increases?
ii) decreases?
i) Blood flow to kidneys (so GFR), aldosterone (Na + water reabsorption + Retention), protein excretion
ii) Serum creatinine, urate + albumin
PREGNANCY PHYSIOLOGY
What can happen in terms of the urinary system?
What is a consequence of this?
What else contributes?
- Dilatation of ureters + collecting system > physiological hydronephrosis (more R)
- Increased risk of UTIs
- Decreased ureter tone/peristalsis = urinary stasis
PREGNANCY PHYSIOLOGY
What 4 forces/pressures govern fluid retention in pregnancy?
- Capillary (hydrostatic) pressure of blood in vessel = draws fluid OUT
- Interstitial fluid colloid oncotic pressure of proteins in interstitial fluid = draws fluid OUT
- Interstitial fluid pressure of tissues surrounding vessel = draws fluid IN
- Plasma colloid oncotic pressure (albumin) = draws fluid IN
PREGNANCY PHYSIOLOGY
Why does pregnancy cause dilutional anaemia?
What is the purpose of this?
- Increased RBC production = higher iron, folate + B12 requirements
- Increased ECF + plasma volume MORE than RBC volume leading to lower red cell conc (haematocrit) + lower Hb conc
- Facilitates placental perfusion
PREGNANCY PHYSIOLOGY
What happens in terms of clotting in pregnancy?
- Clotting factors (fibrinogen, VII, VIII + X) increase
- Plasminogen activator inhibitor increases (plasmin usually breaks clots down)
- Hypercoaguable state
PREGNANCY PHYSIOLOGY
In terms of haematology in pregnancy, what…
i) increases?
ii) decreases?
i) WBCs, ESR, d-dimers, ALP
ii) Platelets, albumin
PREGNANCY PHYSIOLOGY
What are the metabolic changes are there in pregnancy?
- Early = post-prandial glucose plasma peak lower due to fat deposition + glycogen storage
- Late = higher for longer + maternal insulin resistance (via hPL) for foetal glucose sparing
- Maternal insulin rises during most of pregnancy
PREGNANCY PHYSIOLOGY
What are the changes to the skin and hair in pregnancy?
- Linea nigra + melasma
- Striae gravidarum
- General pruritus (?OC)
- Spider naevi + palmar erythema
- PP hair loss normal, improves within 6m
PREGNANCY PHYSIOLOGY
What facilitates blastocyst implantation in pregnancy?
- Increased GFs, proteolytic enzymes + inflammatory mediators
- Not rejected as change in self/non-self pattern recognition molecules (HLA + MHC proteins)
PREGNANCY PHYSIOLOGY
In pregnancy, what changes to the humoral and cell-mediated immunity?
- Humoral = unchanged, plenty of circulating Th2 cells to fight infections (antibodies)
- Cell-mediated = reduced as progesterone down regulates production of Th1 cells (phagocytes, cytotoxic T lymphocytes)
PREGNANCY PHYSIOLOGY
What is the impact of dampening Th1 production?
What are the implications?
- Shift to increased Th2 production (bias) to protect foetus
- Pre-eclampsia, IUGR + miscarriage do not have a Th2 bias
REPRODUCTION
What are the different stages in follicular genesis and what stage in the cell cycle are they?
- Primordial follicles = diploid, arrested at prophase I
- Primary follicle = diploid, undergoing meiosis I
- Secondary follicle = haploid, once meiosis I complete
- Antral (Graafian) follicle = haploid, frozen in metaphase II
REPRODUCTION
What are the structures of…
i) primordial follicles?
ii) primary follicles?
i) Each contain primary oocyte (germ cells) that eventually form mature ovum
ii) Primary oocyte > zona pellucida > cuboidal granulosa cells, zona pellucida secreted from granulosa cells
REPRODUCTION
What happens when follicles reach the secondary follicle stage?
- Granulosa cells express FSH receptors = oestrogen production to grow
- Theca cells express LH receptors = steroidogenesis
REPRODUCTION
How is a dominant follicle chosen?
- Fluid-filled chamber (antrum) starts to develop causing rapid growth
- Rising LH leads to rising oestrogen
- Dominant follicle with lots of FSH receptors outgrows the others
REPRODUCTION
What happens at ovulation?
- LH surge = smooth muscle of theca externa contracts
- Follicle bursts + secretes enzymes puncturing hole in ovary
- Fimbriae of fallopian tubes sweeps oocyte up, surrounded by zona pellucida
- Leftover follicle > corpus luteum
REPRODUCTION
How does fertilisation occur?
- Sperm enters fallopian tube + attempts to penetrate through corona radiata + zona pellucida via acrosome reaction
- Fusion of sperm + egg = zygote
REPRODUCTION
What happens immediately after fertilisation?
- Cell rapidly divides > mass of cells (morula) travels to uterus
- Fluid filled cavity (blastocele) expands to form blastocyst (>80 cells) with outer layer (trophoblast) + inner layer (embryoblast)
REPRODUCTION
When does the blastocyst reach the uterus?
What happens?
- 8–10d after ovulation
- Trophoblast cells undergo adhesion to stroma of endometrium
- Outer layer of trophoblast (syncytiotrophoblast) forms projections into the stroma
REPRODUCTION
Once the blastocyst has implanted, what happens to the stroma?
What signifies blastocyst implantation?
- Cells of stroma convert into decidua to provide nutrients (decidual reaction)
- Syncytiotrophoblast produces hCG to maintain corpus luteum
REPRODUCTION
What happens to the embryoblast after implantation?
- Divides into yolk sac + amniotic cavity on opposing sides with embryonic disc between
- Chorion surrounds this complex with inner cytotrophoblast + outer syncytiotrophoblast which is embedded in endometrium
REPRODUCTION
How does the chorion develop over time?
- Chorionic cavity forms around the yolk sac, embryonic disc + amniotic sac + these structures suspended from the chorion by the connecting stalk (eventually umbilical cord)
REPRODUCTION
When does the embryonic disc develop further?
What does it develop into?
- 5w
- Foetal pole with 3 layers = ectoderm (outer), mesoderm (mid), endoderm (inner)
REPRODUCTION
What tissues does the…
i) ectoderm
ii) mesoderm
iii) endoderm
produce?
i) Skin, hair, nails, teeth, CNS
ii) Heart, muscle, bone, connective tissue, kidneys, blood
iii) GI tract, lungs, liver, pancreas, thyroid, reproductive
REPRODUCTION
When do actual organs begin to develop?
- 6w foetal heart forms + starts to beat
- 8w all major organs start development
REPRODUCTION
How does the placenta develop?
- Syncytiotrophoblast forms chorionic villi with foetal blood vessels
- Those nearest connecting stalk most vascular, cells proliferate + become placenta at about 10w
REPRODUCTION
How is nutrient diffusion facilitated in terms of how the placenta develops?
- Spiral arteries reduce their vascular resistance (narrow bore high resistance > wide bore low)
- Makes them more fragile so blood flows out causing pools of blood (lacunae) at 20w surrounding chorionic villi for diffusion
REPRODUCTION
What role does the placenta play in immunity?
- IgG crosses placenta to give foetus immunity
- Primary immune deficiency hypogammaglobulinaemia can occur in babies whose mothers did not have high enough IgG during pregnancy
REPRODUCTION
What role does the placenta play in respiration?
- Oxygen source for foetus, foetal Hb has higher affinity for oxygen so extracts it from maternal blood
- CO2, H+, HCO3- + lactic acid exchanged to maintain acid-base balance
REPRODUCTION
What role does the placenta play in nutrition and excretion?
- Main source = glucose, can transfer vitamins + minerals as well as alcohol + meds
- Similar function to kidneys, filters foetal waste (urea + creatinine)
REPRODUCTION
What are the main hormones produced by the placenta?
- hCG (maintain corpus luteum)
- Oestrogen
- Progesterone
- Human placenta lactogen
REPRODUCTION
What is the role of oestrogen in pregnancy?
- Softening tissue > more flexible, allows muscles + ligaments of uterus and pelvis to expand + cervix become soft
- Enlarges + prepares breasts + nipples for breast feeding
- E3 declines with foetal distress, E2 increases endometrial progesterone receptors
REPRODUCTION
What is the role of progesterone in pregnancy?
- Produced by corpus luteum until 10w
- Initially prepares endometrium for implantation by proliferation, vascularisation + decidual reaction
- Later, maintains pregnancy by preventing contraction
- Relaxation elsewhere > heartburn, constipation, hypotension
REPRODUCTION
What is the role of human placental lactogen in pregnancy?
- Diabetogenic as raises blood glucose levels to help increase nutrient supply + helps convert mammary glands into milk secreting tissue
MENSTRUAL CYCLE
When is the last menstrual period?
- 1st day of last period (cycle runs from 1st day of last to 1st day of next
MENSTRUAL CYCLE
What 2 cycles exist within the menstrual cycle?
- Ovarian cycle (development of follicle + ovulation)
- Uterine cycle (functional endometrium thickens + shreds)
MENSTRUAL CYCLE
What happens in the menstrual phase?
- Old endometrial lining from previous cycle shed marking day 1 (lasts 5d)
MENSTRUAL CYCLE
What happens in the follicular phase?
- Independently primordial follicles mature into primary + secondary follicles with FSH receptors
- Low oestrogen + progesterone = pulses of GnRH > LH + FSH release
- FSH leads to follicular development + recruitment
MENSTRUAL CYCLE
What happens as secondary follicles grow during follicular phase?
- Theca cells develop LH receptors + secrete androgens
- Granulosa cells develop FSH receptors + secrete aromatase
- Leads to increased oestrogen > -ve feedback on pituitary to reduce LH + FSH leading to some follicles to regress
MENSTRUAL CYCLE
What occurs during ovulation?
- Follicle (dominant) with most FSH receptors continues developing
- Secretes further oestrogen which at a threshold causes spike in LH (+ slight rise in FSH) causing release of ovum on day 14
MENSTRUAL CYCLE
What occurs during the luteal phase?
- Dominant follicle > corpus luteum + luteinised granulosa cells converts cholesterol into progesterone for 10d to facilitate implantation + reduce FSH/LH + oestrogen
- Also secretes inhibin to reduce FSH
MENSTRUAL CYCLE
What happens if the egg is fertilised?
- Syncytiotrophoblast of embryo secretes human chorionic gonadotropin (hCG) which maintains corpus luteum
MENSTRUAL CYCLE
What happens if the egg is not fertilised?
- hCG absence > corpus luteum degenerates into corpus albicans
- Fall in progesterone + oestrogen causes endometrium to breakdown + menstruation occurs
- FSH + LH levels rise
- Stromal cells of endometrium release prostaglandins to encourage endometrium breakdown + uterine contraction
MENSTRUAL CYCLE
What happens in the early secretory phase of the menstrual cycle?
- Progesterone mediated + signals ovulation occurred to make endometrium receptive, cause spiral arteries to grow longer + uterine glands to secrete more mucus
MENSTRUAL CYCLE
What happens in the late secretory phase of the menstrual cycle?
- Cervical mucus thickens + less hospitable for sperm
- Decrease in oestrogen + progesterone > spiral arteries collapse + constrict + functional layer prepares to shred
MENSTRUAL CYCLE
What are the stages of the menstrual cycle?
- Menstruation (Days 1-5)
- Proliferation (Days 6-14)
- Ovulation (Day 14)
- Secretion (Days 16-28)
MENSTRUAL CYCLE
What happens in the proliferative phase?
- High oestrogen > thickening of endometrium, growth of endometrial glands + emergence of spiral arteries from stratum basalis to feed the functional endometrium
- Consistency of cervical mucus changes to make more hospitable for sperm