Introduction Flashcards
Pregnancy is divided into 3 trimesters
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What are some maternal changes that can occur with pregnancy?
- Increased weight [3rd]
- Increased blood volume [2nd & later]
- Increased blood clotting tendency [2nd & later]
- Decreased blood pressure [2nd]
- Altered brain function [1st & later]
- Altered hormones [1st & later]
- Altered appetite (quantity and quality) [1st & later] – GI imbalance
- Altered fluid balance [2nd & later]
- Altered emotional state [1st & later]
- Altered joints [3rd]
- Altered immune system [1st & later]
main risk to maternal health = linked to
delivery
note: at early stage of pregnancy, low risk to mother
what is meant by conceptus?
everything resulting from the fertilised egg (baby, placenta, fetal membranes, umbilical cord)
NOTE: progesterone levels remain high during delivery –> but falls sharply AFTER delivery
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When do we start counting pregnancy?
- from first day of last menstrual period
- -> because we dont know when ovulation is
- -> normal pregnancy = 38 - 42 weeks gestational age
what is a cotyledon?
what is the significance of a cotyledon?
functional subunits of the placenta
- -> contains placental villus (which branches out)
- -> gives large SA
- (to absorb nutrients from maternal blood to fetal blood)
- to remove waste productions (deoxygenated blood / urea etc. from fetal blood)
umbilical artery –> baby to mother
umbilical vein –> placenta to baby
What are significant features of the placenta?
- highly branched structure –> provides a large surface area (~11m2).
- effective for transport of molecules between maternal and fetal circulations.
- Anchors the placenta (and hence the baby) for 9 months.
- Intimate contact between maternal and placenta tissues – interesting immunology!
What are the placental functions?
Functions:
Separation
–> separates blood of mother + fetus
Exchange
–> of nutrients and waste products
Biosynthesis
–>
Immunoregulation
–> so that mother’s immune system doesn’t reject the fetus
Connection
–> provide physical connection between mother and fetus
Describe the development of the placenta?
Starts as a layer of single cells in the blastocyst
- which then proliferate + differentiate
- to form a simple branched structure that expands iteratively
Describe the development of the placenta?
Starts as a layer of single cells in the blastocyst
- which then proliferate + differentiate
- to form a simple branched structure that expands iteratively
contact between fetal and maternal tissues
- spiral artery = blocked by cytotrophoblast shell
- if cytotrophoblast cells break down –> fetus = exposed to high pressure maternal blood –> may cause miscarriage (due to unstable anchoring)
What is the significance of cytotrophoblast shells + spinal arteries during fetal development?
- Cytotrophoblast shell limits blood (oxygen) supply to embryo during early development
- Remodelling of spiral arteries –> allows high volume blood supply in trimesters 2 and 3, when infant growth is greatest.
Placental mal-development (4 things)
Miscarriage (late first trimester)
Miscarriage (second trimester)
Pre-eclampsia (early delivery)
Fetal growth restriction (small infant)
define labour
- uterus is undergoing regular fundally dominant contractions
- and cervix is undergoing ripening and effacement
Describe tof process of labour - dependent of gestational stage.
- Cervical ripening and effacement (increasing)
- Co-ordinated myometrial contractions (increasing)
- Rupture of fetal membranes
- Delivery of infant
- Delivery of placenta
- Contraction of uterus
What are the 3 labour stages and how long do they last ?
- phase 1 = many hours
- -> when cervical changes occur+ contraction begins
- phase 2 = hours
- -> delivery of baby
- phase 3 = 30 mins
- -> delivery of the placenta
first trimester = week
second trimester = week
third trimester = week
first trimester = 13 week
second trimester = 26 week
third trimester = 39 week
What initiates labour? during:
a) term
b) preterm
What initiates labour? during:
a) term
- -> oestrogens
- -> low progesterone
- -> CRH
- -> Oxytocin
- -> (but not rly sure)
b) preterm
- -> Intrauterine infections
- -> intrauterine bleeding
- -> multiple pregnancy
- -> stress
- -> others
During the labour process, what happens to the cervix
there is :
Cervical ripening and effacement
- Change from rigid to flexible structure
- Remodelling (loss) of extracellular matrix
- Recruitment of leukocytes (neutrophils)
- Inflammatory process
- -> Prostaglandin E2, interleukin-8
- -> Local (paracrine) change in IL-8
During the labour process, what happens to the myometrium?
there is:
- Co-ordinated myometrial contractions
- Fundal dominance
- Increased co-ordination of contractions
- Increased power of contractions
Key mediators
- -> Prostaglandin F2a (E2) levels increased from fetal membranes
- -> Oxytocin receptor increased
- -> Contraction associated proteins
During the labour process, what happens to the fetal membranes?
there is:
Rupture of fetal membranes
- Loss of strength due to changes in amnion basement component
- Inflammatory changes, leukocyte recruitment
- -> Modest in normal labour, exacerbated in preterm labour
- Increased levels and activity of MMPs
- Inflammatory process in fetal membranes
NOTE:
Cervix
Prostaglandin E2, interleukin-8, MMPs
Myometrium
Prostaglandin F2a (E2) levels increased from fetal membranes
Oxytocin receptor increased
Contraction associated proteins
Fetal membranes
Inflammatory process in fetal membranes
PGs, interleukins, MMPs
-
during Labour, many initiators act on NFkB –> causes up regulation of inflammatory genes
- IL-1B = can further drive NFkB levels
- Activators of inflammations = linked with preterm labour (e.g intrauterine infection)
-
Supporting evidence
Almost all pro-labour genes have _____ binding domains in their promoters
Modification of NFkB sites in promoter sequences leads to __________
Almost all pro-labour genes have NFkB binding domains in their promoters
Modification of NFkB sites in promoter sequences leads to loss of expression in cells or in expression vectors
CRH + PAF = key drivers of labour
–> unregulated inflammatory pathways in fetal membranes
-
PGE2 has important role in =
cervical ripening
- 3 weeks before delivery ____ levels rise
CRH increases
why is platelet activating factor important in the process of labour?
PAF = Part of lung surfactant
- -> Produced by maturing lung, before birth
- -> PAF Levels in amniotic fluid increase near term
- -> Fetal signal of maturity
describe the hypothesis for parturition
- lungs mature –> produce PAF
- placenta = source of CRH –> increases CRH production –> CRH goes to baby –> stimulate pit gland –> increase acth release —> activate adrenal gland –> cortisol produced–> activates lung –> ALSO goes to placenta –> increases CRH levels
- DHEASE = precursor to oestrogen
NOTE
- Anything that increases CRH may predispose to labour (stress, multiple infants)
- Anything that increases muscle contraction may predispose to labour (excess stretch of uterus)
- Anything that activates inflammatory cascades may predispose to labour
- The above apply to preterm labour (intrauterine infection, bleeding, twins)
-
What happens if you give Progesterone receptor blockade to a pregnant woman?
pregnancy loss
during pregnancy –> a lot of progesterone receptors re released –> binds to NFkB –> stops it from initiating proinflammatory action
PR-B mediates the main effects of progesterone via gene expression
PR-A is less able to mediate these effects
Ratio of PR-A : PR-B increases at term
???
Loss or change in PR may lead to
‘functional progesterone withdrawal’
What is a key regulator of labour?
NFkB
