Pregnancy, Parturition and Late fatal development Flashcards

1
Q

Describe how fetal growth changes overtime? what drives the growth at each stage and what is it reliant on

A

Embryo-fetal growth during the 1st trimester is relatively limited

  • Early nutrition is histiotrophic
  • Reliant on uterine gland secretions and breakdown of endometrial tissues (by syncytiotrophoblasts)

Switch to haemotrophic support at start of 2nd trimester

  • fetus derives nutrients from maternal blood
  • Hence rate of growth of fetus increases exponential

Achieved via a haemochorial-type placenta where maternal blood directly contacts the fetal membranes.

  • Develop in 12th week gestation
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2
Q

what are uterine galnd secretions a source of in histiotrophic nutrition

A

Endometrial milk-

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3
Q

How does early embryo derive nutrition?

A

Syncytiotrophoblasts invade endometrium

  • uses breakdown products from tissue to support embryo
  • secretions from uterine glands
  • breakdown of maternal capillaries results in the syncytiotrophoblasts being exposed to the maternal blood
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4
Q

What is the amnion? what does it form eventually and when

A
  • Derivative of the epiblast
  • however does not go on to form part of the foetus- extraembryonic
  • The first of the fetal membranes
  • Forms the amniotic cavity through secretion from amniotic cells
  • eventually becomes the amniotic sac which surrounds the developing foetus through 2nd/3rd trimester
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5
Q

What are the following derived from?:

  1. Yolk sac
  2. Amnion
A
  1. hypoblast
  2. epiblast
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6
Q

What are ALL the fetal membranes? give their features and contrast them

A

Extraembryonic tissues that form a tough flexible sac surrounds the fetus and forms the basis of the maternal-fetal interface

Amnion
> arises from the epiblast
> forms a closed, avascular sac with the embryo at one end
> begins to secrete amniotic fluid from 5th week - forms a fluid filled sac that encapsulates and protects the fetus

Chorion
> formed from yolk sac derivatives and the trophoblast
> highly vascularized
> gives rise to chorionic villi - outgrowths of cytotrophoblast from the chorion that form the basis of the fetal side of the placenta

Yolk sac
> derived from hypoblast

Allantois
> outgrowth of the yolk sac
> grows along the connecting stalk from embryo to chorion
> becomes coated in mesoderm and vascularizes to form the umbilical cord

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7
Q

How ELSE is the allantosis important in the embryo

A

May contribute to the bladder of the embryo

May be important to remove toxins from embryo

Combination of allantosis, mesoderm and connecting stalk form the umbilical cord

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8
Q

How does the amniotic sac develop? what are the layers of the amniotic sac

A
  • Expansion of the amniotic sac by fluid accumulation forces the amnion into contact with the chorion, which fuse, forming the amniotic sac
  • Amniotic sac: 2 layers; amnion on the inside, chorion on the outside
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9
Q

What is the chorion?

A
  • outer membrane in extraembryonic membranes
  • surrounds the conceptus unit
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10
Q

What is the connecting stalk?

A
  • part of extraembryonic tissue
  • links the developing embryp to the chorion
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11
Q

What are the trophoblastic lacunae and how does it contribute to the origins of the placenta?

A

As the syncytiotrophoblasts invade endometrium, maternal capillaries and glands are broken down

Lumens of capillaries and glands start to fuse

This creates a continuous space through which maternal blood flows

become intervillous spaces or maternal blood spaces

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12
Q

Describe phases of chorionic villus formation

A

Primary: outgrowth of the cytotrophoblast through syncitiotrophoblasts and branching of these extensions

Secondary: growth of the fetal mesoderm into the primary villi

Tertiary: growth of the umbilical artery and umbilical vein into the villus mesoderm, providing vasculature.

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13
Q

What is the structure and function of chorionic villi?

A

Finger-like extensions of the chorionic cytotrophoblast, which then undergo branching

Provide substantial surface area for exchange

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14
Q

Describe the microstructure of terminal villi and describe it’s purpose

A
  • Convoluted knot of vessels and vessel dilation
  • Slows blood flow enabling exchange between maternal and fetal blood
  • Whole structure coated with trophoblast
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15
Q

How does the structure of terminal villi change over pregnancy?

A

Early pregnancy:

  • 150-200µm diameter,
  • approx. 10µm trophoblast thickness between capillaries and maternal blood.

Late pregnancy:

> villi thin to 40µm, vessels move within villi to leave only 1-2µm trophoblast separation from maternal blood.

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16
Q

Describe maternal blood supply to the endometrium- give details of the anatomical branching.

A

Uterine artery branches give rise to a network of arcuate arteries.

Radial arteries branch from arcuate arteries, and branch further to form basal arteries.

Basal arteries form spiral arteries during menstrual cycle endometrial thickening.

U A R B S

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17
Q

How does uterine blood supply change through the menstrual cycle?

A

Basal arteries during proliferative stage grow and spiralize to produce spiral arteries

if implantation does not occur, endometrium is lost and spiral arteries regress

if implantation does occur, spiral arteries stabilise and provide maternal blood supply to the fetus

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18
Q

Describe spiral artery remodelling. Draw if possible . what is the result of this remoddeling process?

A

Extensive during implantation and placental development

Extra-villus trophoblast (EVT) cells coating the villi invade down into the maternal spiral arteries, forming endovascular EVT

  • endothelium and smooth muscle is broken down
  • EVT replaces these and coats inside of vessels
  • EVT cells despiralise the capillaries to open them into straight channels

This leads to Conversion: turns the spiral artery into a low pressure, high capacity conduit for maternal blood flow

This process may underlie issues such as preeclampsia and intra-uterine growth retardation

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19
Q

Describe the structure of placenta

A

Maternal unit

  • maternal blood supply and spiral arteries
  • supply maternal blood spaces with blood
  • drains via maternal vein

Fetal side
> chorionic villus
> invasion of fetal artery and vein into villi

20
Q

How does nutrient exchange across the placenta occur?

Describe the process for each molecule

(Ca? Amino acids? glucose? electrolytes?)

A

nutrient specific
Oxygen: diffusion (high maternal O2 tension, low fetal O2 tension)

Glucose: facilitated diffusion by transporters on maternal side and fetal trophoblast cells.

Water: placenta main site of exchange, though some crosses amnion-chorion. Majority by diffusion, though some local hydrostatic gradients.

Electrolytes: lots of sodium and other electrolytes across the placenta - combination of diffusion and active co-transport.

Calcium: actively transported against a concentration gradient by magnesium ATPase calcium pump.

Amino acids: reduced maternal urea excretion, converted to AA and active transport of amino acids making up urea to fetus

21
Q

Describe the physiological changes to circulation in pregnancy for BOTH mother and fetus

A

Maternal changes:

  • Maternal cardiac output increases 30% during first trimester (stroke vol & rate)
  • TPR decreases up to 30%
  • Blood volume increases to 40% as RBC and plasma also increase
  • Pulmonary ventilation increases 40%

Placenta and Fetus:

  • Placenta consumes 40-60% glucose and O2 supplied
  • But although fetal O2 tension is low, O2 content and saturation are similar to maternal blood.
  • Embryonic and fetal hemoglobins: greater affinity for O2 than maternal hemoglobin.
22
Q

Describe the Organ maturation process of the Circulatory and Respiratory system

A

In 2nd/3rd trimester

Circulatory system
• begins with tube of mesoderm pumping blood from day 22
• placenta acts as site of gas exchange for fetus
• ventricles act in parallel rather than series
• vascular shunts bypass pulmonary & hepatic circulation -> closed at birth
• allows efficient pumping of placental blood

Respiratory system
• start as lung buds
• primitive air sacs form in lungs around 20 weeks, vascularization from 28 weeks
• surfactant production begins around week 20, upregulated towards term
• fetus spends 1-4h/day making rapid respiratory movements during REM sleep (practicing)

23
Q

Describe the Organ maturation process of the GI and Nervous system.

GI: when does pancreas and liver function start ans what happens to amniotic fluid

Neuro: movement and consciousness

A

Gastrointestinal system
• gut tube formed from endoderm
• endocrine pancreas functional from start of 2T, insulin from mid-2T
• liver (day 23) glycogen progressively deposited - accelerates towards term
• large amounts of amniotic fluid swallowed -debris and bile acids form meconium (delivered after birth)

Nervous system
• fetal movements begin late 1T, detectable by mother from ~14 weeks
• stress responses from 18 weeks, thalamus-cortex connections form by 24 weeks
• fetus does not show conscious wakefulness - mostly in slow-wave or REM sleep

24
Q

What is organ maturation coordinated by?

what else also increases?

A

fetal corticosteroids

  • increase towards the end of pregnancy
  • increase in lecithin (surfactant) and liver glycogen in parallel with increase in corticosteroids
25
Q

What is the process of labour? give a brief overview

A
  • Safe expulsion of the fetus at the correct time
  • Expulsion of the placenta and fetal membranes
  • Resolution/healing to permit future reproductive events
26
Q

what type of reaction is characteristic in. labour; explain in detail histologically

A

pro-inflammatory reaction

  • Immune cell infiltration into femal repro tract
  • Inflammatory cytokine and prostaglandin secretion (orchestrate timing and sequence of labour)
27
Q

Summarise and explain the phases of labour

A

Phase 1 - quiescence

  • uterus is quiet
  • no contraction
  • cervical softening occurs
  • late 1st trimester

Phase 2 - activation

  • uterine preparation
  • cervix becomes ready to dilate

Phase 3 - stimulation

  • uterine contraction
  • cervical dilation
  • fetal and placenta expulsion
  • (three stages of labour)

Phase 4 - involution

  • restoration of uterus to original size
  • repair of cervix
  • onset of lactation
28
Q

What are the 3 stages of labour? in phase 3

A

First Stage:

Contractions start and Cervix dilation.

Has 2 phases in it

  • Latent Phase: Slow dilation of the cervix to 2-3cm
  • Active Phase: Rapid dilation of the cervix to 10cm

longest phase

Second stage:

• Delivery of the fetus

  • Commences at full dilation of the cervix (10cm)
  • Maximal myometrial contractions

Third stage:

• Delivery of the placenta

  • Expulsion of placenta and fetal membranes
  • Post-partum repair
29
Q

How long does delivery take?

A

First delivery: 8-18h

Subsequent deliveries: 5-12h

30
Q

What is the role of the cervix in pregnancy and how does it achieve this?

A
  • Retains the fetus in the uterus
  • High connective tissue content: this makes it rigid and strecthc resistant
  • it has Bundles of collagen fibres embedded in a proteo-glycan matrix
31
Q

What happens during re-modelling of the cervix from 1st trimester to post partum repair

S R D P

A

Softening - begins in 1st trimester

  • Measurable changes in compliance but retains cervical competence; cervix is still closed


Ripening - weeks and days before birth

  • Monocyte infiltration
  • IL-6 and IL-8 secretion
  • Hylaluron deposition


Dilation - increased elasticity

  • Increased hyaluronidase expression -> HA breakdown
  • MMPs decrease collagen content


Post-partum repair
• Recovery of tissue integrity and competency
• Ensures woman can become pregnant again

32
Q

What are some hormones thought to be involved in the endocrine regulation of labour

A
  • CRH
  • estrogen and progesterone
  • oxytocin

*still relatively unclear as to the exact hormone which initiates labour

33
Q

Describe the role of CRH in labour.

what happens to it’s levels and describe it function in labour

A

Current thinking: fetus determines timing of parturition through changes in fetal HPA axis

CRH levels rise exponentially towards the end of pregnancy

Decline in CRH binding protein levels, so CRH bioavailability increases

CRH functions in labour:

  • promotes fetal ACTH and cortisol release
  • increasing cortisol drives placental production of CRH → Positive feedback!
  • stimulates DHEAS production by the fetal adrenal cortex → substrate for estrogen production
34
Q

Describe the role of estrogen and progesterone in labour

A

High progesterone in pregnancy maintains uterine relaxation

Serum estrogen:progesterone ratio may shift in favour of estrogen - this is unclear

As term approaches, switch from PR-A isoforms (activating) to PR-B and PR-C (repressive) isoforms expressed in the uterus → functional progesterone withdrawal

Rise in Estrogen Receptor Alpha expression

  • Uterus becomes ‘blinded’ to progesterone action and sensitised to estrogen action
  • Control of these changes unclear but likely leads to local changes in E:P ratio in uterine tissues
35
Q

What are the roles of progesterone DURING pregnancy?

A

promotes implantation

  • suppresses maternal immune response to fetal antigens, thus preventing rejection of the fetus
  • cardiovascular compliance
  • provision of substrate for manufacture by the fetal adrenal of glucocorticoids and mineralocorticoids
  • maintenance of uterine quiescence through gestation
  • a role in parturition
36
Q

Describe the structure and production of oxytocin- how does the production chnages across pregnancy

A

Nonapeptide (9aa) hormone synthesized mainly in the utero-placental tissues and pituitary

Uterine oxytocin production increases sharply at onset of labour - driven by increase in estrogen levels locally (change in E:Prog ratio)

Pituitary release promoted by stretch receptors → Ferguson reflex

37
Q

What is the Ferguson reflex? Draw it

A

maternal urge to push

Fetus starts to bear down on the cervix

Stretch receptors in cervix and vagina signal up to the hypothalamus

Firing of hypothalamus onto the posterior pituitary increases

Triggers release of oxytocin from posterior pituitary into maternal circulation

Acts on uterus and myometrium

38
Q

How does oxytocin signal; explain the signalling pathway.

what factors increase and decrease it?

A
  • signals through G-coupled oxytocin receptor (OTR / OXTR)
  • Pre-labour: progesterone inhibits OXTR expression -> uterus relaxed
  • Rise in estrogen promotes large increase in uterine OXTR expression
39
Q

What are the functions of oxytocin in labour?

A
  • Increases connectivity of myocytes in myometrium (syncytium) - promotes formation of gap junctions
  • Destabilise membrane potentials to lower threshold for contraction
  • Enhances liberation of intracellular Ca2+ ion stores - aids contraction
40
Q

Describe the production of prostaglandins (PGs) during labour; i.e. what PGs are made and what factors affect it’s release

A

Primary PGs synthesised during labour are PGE2, PGF2alpha and PGI2.

Rising estrogen levels drive prostaglandin action in the uterus in two ways:

  1. Rising estrogen activates phospholipase A2 enzyme, generating more arachidonic acid for PG synthesis
  2. Estrogen stimulation of oxytocin receptor expression promotes PG release
41
Q

Describe the role of the different types prostaglandins in labour

A

PGE2 - cervix re-modelling

  • Promotes leukocyte infiltration into the cervix, IL-8 release and collagen bundle re-modelling

PGF2alpha - myometrial contractions

  • Destabilises membrane potentials and promotes connectivity of myocytes (with Oxytocin)

PGI2 - myometrium

  • • Promotes myometrial smooth muscle relaxation and relaxation of lower uterine segment - important to allow blood flow to return into the uterus and placenta

Other factors: peptide hormone relaxin and nitric oxide (NO) implicated in cervix re-modelling

42
Q

what other factors are implcated in cervix remodelling

A

relaxin and NO

43
Q

Summarise the integrated regulation of labour. Draw it

A
44
Q

Describe myometrial contractions during labour; how does it relate to the syncytium and what does it implicate in pregnancy

A
  • Myometrial muscle cells form a syncytium (extensive gap junctions) to transmit contractions
  • Contractions start from the fundus, spread down upper segment
  • Muscle contractions are brachystatic -fibres do not return to full length on relaxation
  • This causes lower segment and cervix to be pulled up forming birth canal
45
Q

Describe the process of fetal expulsion- summarise

A

Head engages with pelvic space 34-38wks

Pressure on fetus causes chin to press against chest (flexion)

Fetus rotates (belly to mother’s spine)

Head expelled first after cervix dilates

Shoulders delivered sequentially (upper first) followed by torso.

46
Q

The final stage of labour

Describe the placental expulsion and repair process

A

Rapid shrinkage of the uterus after delivery causes area of contact of placenta with endometrium to shrink

Uterine shrinkage also causes folding of fetal membranes - which then peel off the endometrium

Clamping of the umbilical cord after birth stops fetal blood flow to placenta, then villi collapse

Hematoma formation between decidua and placenta

Contractions expel placenta and fetal tissues (occur with haematoma)

47
Q

The final phase of labour

Explain what process to restore the uterus to it’s non-pregnanat state

A

Uterus remains contracted after delivery to facilitate uterine vessel thrombosis in order to prevent interuterine bleeding

Uterine involution and cervix repair restore non-pregnant state. This:

  • Shields uterus from commensural bacteria in repro traxct
  • Restore endometrial cyclicity in response to hormones