Parturition &lactation Flashcards
Define parturition
- Process of giving birth ‘to be in labour’
- Involves softening & effacement of the cervix and development of uterine contractions( rupture of membranes not essential)
Outline the stages of labour
- ) INITIAL (LATENT) PHASE: Contractions develop, cervix softens &effaces (days)
- )ACTIVE PHASE: Regular contractions (~3 every 10mins) & steady dilation of the cervix (~3-4cm to 10cm)
- )STAGE 2: cervix fully dilated-10cm; strong propulsive contractions 1-2hours
- ) STAGE 3: placenta delivered (oxytocin important)
What else may be given to a woman if oxytocin is insufficient in delivering the placenta
-Clinically women may be given ergotocin & oxytocin mix to allow artificial contraction of the uterus in case the oxytocin is insufficient
Describe the quiescent stage of pregnancy
<37weeks
- During this stage the cervix &membranes are intact
- Closed cervix maintains pregnancy and acts as a barrier to ascending infection
- The cervix is elastic tissue with some smooth muscle; collagen fibres in a proteoglycan matrix
- There is also epithelia cell lining and a mucous plug
Outline the preparation of the cervix& fetal membranes for labour (activation and stimulation)
-PGE2 is used for induction. This causes membrane weakening and rupure, causing cervix ripening to begin and allowing the cervix to dilate
INFLAMMATORY PROCESS:
-iNOS, COX-2, prostaglandin production (PGE2), matrix metalloproteinases 2&9(these break down the collagen), cytokines and immune cells
-Cervix softens and more likely to dilate/efface; ready for labour
What instigates the inflammatory process?
Hormone changes: functional progesterone withdrawal—> inflammation &influx of immune cells,increased corticotrophin releasing hormone & oestrogen, plus cervical distension —> oxytocin—>PGR (Ferguson reflex)
How is the myometrium prepared for pregnancy?
-At the quiescent stage the myometrium is dense smooth muscle cells embedded in connective tissue & well vascularised. It is sparsely innervated in pregnancy
-To get to the activation / stimuation stage….
-There’s induction of ‘contraction associated proteins; prostaglandin receptor COX-2, oxyotcin receptor, gap junctions (connexins), calcium signalling proteins & ion channels
-Myometrium primed for contraction
-activation with some uterine activity
powerful effective contractions stimulate it
What causes preparation of the myometrium for pregnancy?
- CRH
- oestrogen
- oxytocin
- uterine distension
- function progesterone withdrawal-inflammation &influx of immune cells
- prostaglandins from the fetal membranes
What is Nifedipine used for in labour
- used to treat pre-term labour
- It is an L-type ca2+ channel blocker so targets the voltage gated ca2+ channels to stop contraction
How does the contractile interval change during pregnancy?
-Decreases as the woman comes to term
How does the resting membrane potential change during pregnancy?
-Gets less negative so it’s more likely to be excited and more likely to contract at the end of pregnancy
What is the clinical application of PGE2?
-Used to ripen the cervix
Outline the functions of gap junctions& connexins in pregnancy
-Gap junctions made from connexin proteins(Cx)
-Cx43 & Cx26 up-regulated during labour—> allows for better transmission of signals between cells
Increased gap junctions results in:
-Intercellular communication
-More powerful contractions
Outline the role of oxytocin in labour
- Important uterotonin in labour
- Increased uterine sensitivity to oxytocin at term
- Increased expression of oxytocin receptor mRNA & protein towards term and peak after onset of labour
Which hormone is thought to be the placental clock?
- CRH
- As the placenta matures it starts pumping out CRH
Why must time of delivery be relatively tightly controlled?
- Babies need to be born at the right time as if not the mother will no longer be able to provide adequate support
- The placenta ages over time so there will be a risk of insufficient nutrients
- All the babies are delivered by 42 weeks, as if not then medical intervention would result
What initiates/times labour in humans ?
- Fetal HPA axis involvement, but progesterone drop not apparent. Evidence for ‘functional’ progesterone withdrawal
- Increasing oestrogen concentrations
- Anecephaly& fetal adrenal gland hypoplasia association with prolonged gestation
Describe the circulating placental steroid hormone levels during pregnancy in humans
- Steady rise in Estradiol (E2) across gestation
- Steady rise with plateau at term in progesterone
- Steady rise in human placental lactogen
- No decrease in progesterone at term
Outline the Ferguson reflex(PGR)
- A neuro-endocrine reflex
- A +ve feedback mechanism involving oxytocin
- Estrogen from ovaries–> Induces oytocin receptors on uterus—> stimulates placenta to make—> prostaglandins which stimulate more contractions of uterus—> positive feedback causing oxytocin release
- Oxytocin from fetus and mother’s posterior pituitary stimulates the uterus to contract
- Initiated by pressure at the cervix or vaginal walls
List the important signals in human parturition
-Fetal hypothalamus activity increases–> increased CRH production–> increased ACTH production
-Fetal adrenal gland increases cortisol & dehydroepiandrosterone sulphate (DHEAS)
-Increased placental CRH & Estrogens
-Reduced progesterone responsiveness ( increased PRA:PRB ratio)
Inflammation:
-Fetal membranes increase COX-2 and increase prostaglandin production
What is the function of DHEAS?
- Can get over to the placenta
- Gets converted to oestrogen
When do the lobules/alveoli grow for milk production
- They grow during early pregnancy to make more milk-producing cells
- Human alveoli adequately differentiated to produce milk from 16 weeks gestation & prolactin is being produced
- But full lactation doesn’t occur until post partum period
Outline how milk is pushed to the nipple
Milk production— Baby suckles— contraction of myoepithelial cells around the alveoli— pushes the milk to the nipple
Describe the hormonal changes that occur at the onset of lactation
- Prolactin is secreted from 16 weeks but breast tissue is unresponsive due to a steroid block
- Withdrawal of oestrogen & progesterone are essential
- Prolactin also drops (suppressed by oestrogen & progesterone) but a steady production maintained (if no suckling-small amount of milk produced 3-4weeks)
- Suckling ensures prolactin secretion; full lactogenesis
What is the link between prolactin & VIP
VIP is a prolactin releasing factor
What is the link between prolactin & dopamine?
Dopamine is a prolactin inhibitory factor
How does suckling ensure milk production?
- ) Neuroendocrine reflex
- ) Suckling:
- Stimulates production of Vasoactive Intestinal Peptide
- Reduces dopamine release - ) Strength &duration of suckling determines amount of prolactin released from the anterior pituitary
- This determines amount of milk made to be available for subsequent feeds
Outline the milk ejection reflex
- Milk is transported from alveoli to nipple
- Neuroendocrine reflex
- Suckling stimulates paraventricular & supraoptic nuclei to produce and release oxytocin (from posterior pituitary)
- Oxytocin causes contraction of myoepithelia cells surrounding alveoli full of milk
- Milk propelled into ducts and intramammary pressure builds up
- Milk spurts through nipple
- Response can be conditioned
