Parturition Flashcards
1
Q
Parturition
A
Process by which conceptus is expelled from the uterus
- Fetus dictates when it comes out, not the mother
- Conceptus consists of: foetus, placenta & foetal membranes
- Parturition requires: simultaneous cervical remodelling & Co-ordinated myometrial contractions
2
Q
Stages of Labour
A
- 1st stage: Regular uterine contractions, cervical mucous plug removed, cervical shortens & dilates- can be particularly long in human/ bitch
- Latent phase: cervix slowly dilates to 3cm (human)
- Active phase: rapid dilation of cervix
- 2nd stage: complete delivery of foetus, rupture of membranes & abdominal contractions
- 3rd stage: placental expulsion
3
Q
Myometrial Contractions
A
Myometrium consists of smooth muscle fibres, nerves, blood & lymph
In pregnancy, oestrogens induce muscle cell hypertrophy (50 to 500μm) ↑ force of contraction
Muscle cells behave as a syncytium being electrically coupled via gap junctions–> simultaneous activation of all the SM cells –> coordinated uterine contraction
4
Q
How the Myometrium contracts
A
- Progesterone hyperpolarises the myometrial membrane–> harder to reach threshold potential (-50 mV)
- Spontaneous depolarizing pacemaker potentials occur-If magnitude of these potentials > critical threshold–> burst of APs is superimposed on the pacemaker potentials–> ↑ in intracellular Ca+2 occurs which binds to regulatory sites on actin & myosin allowing expression of ATPase activity–> contraction
5
Q
Direct Regulation of Myometrial Contraction
A
- Oxytocin – Lowers the excitation threshold of muscle cells
- Prostaglandins – Stimulates liberation of Ca+2 from intracellular stores
6
Q
Contraction- Frequency
A
- At onset of labour large contractions occur which progressively ↑ in frequency & amplitude
- Pressure ↑ from 10mmHg between contractions to 50-100mmHg
7
Q
Brachystasis
A
- Contractions –> retraction of the lower uterine segment & cervix upwards –>Creating a birth canal
- Myometrial cells undergo brachystasis (contract & shorten, but don’t regain original relaxed length)
- Uterine muscles retract, uterine wall thickens & uterine volume ↓–> forces the fetus out
- Uterus divided into 2 segments: Upper segment (contractions), Lower segment (passive, no contractions)
- Retraction ring= Junction between 2 segments- palpation provides ongoing index of labour progression
8
Q
Cervical Remodelling
A
- Cervix has high CT content: Collagen fibre bundles & proteoglycan matrix
- CT resists stretch, allows distension of body of uterus whilst maintaining cervix in a closed state
- Collagen is made up of helical strands of amino acids bound together to form fibrils
- For delivery, cervical remodelling is needed, divided into 4 distinct, but overlapping phases:
- Softening–> Ripening –>Dilation–> Postpartum repair
9
Q
Cervical Softening
A
- The process of softening starts during the first trimester (a measurable decrease in tissue compliance)
- Softening involves a gradual change in the intercellular matrix – NOT very well understood!
- Reduction of collagen fibres
- Structural changes to collagen: ↑GAG as pregnancy proceeds –> ↓aggregation of collagen fibres
- keratin sulphate (which does not bind collagen) increases the most
- dermatan sulphate (which binds very tightly to collagen) ↓
10
Q
Cervical Ripening
A
- For the fetus to move out of the uterus, the softened cervix must “ripen“ & subsequently “dilate”
- Cervical ripening occurs rapidly in the days before birth = maximal loss of tissue compliance & integrity
- It seems “like” a pro-inflammatory reaction:
- ↑ vascularization, Influx of monocytes, ↑ level of IL6 & IL8
- A GAG, high molecular weight forms of hyaluronan (HA) ↑ during ripening & as dilation gets underway, the low molecular weight forms of HA ↑ due to an ↑ in hyaluronidase
11
Q
Cervical Dilation
A
- Involves ↑ in: viscoelastibility, tissue distensibility, hydration, disorganization of the collagen matrix & levels of matrix metaloproteinases
12
Q
Hormonal Control of Cervical remodelling
A
- Prostaglandins are thought to regulate cervical softening – mechanism= unknown
- The cervix produces: prostaglandin E2 (PGE2), prostacyclin (PGI2). prostaglandin F2α(PGF2α)
- Production of prostaglandin increases at term and during parturition
- Application of PGE2 & PGF2α to the vagina or cervix induces cervical compliance
- PGs might facilitate cervical compliance by:
- Inducing collagen breakdown
- Altering GAG/proteoglycan composition
- Inducing leucocytic migration by causing release of IL8
- Nitric Oxide- another possible agent that induces cervical ripening as inhibition of iNOS prevents ripening & NO induces release of PGs
- Relaxin- essential for cervical softening in the sow- not absolutely essential in other species (tends to be PGs)
- CL= Major source of relaxin (↑ risk of premature delivery in women with multiple CL after superovulation)
13
Q
Regulation of Prostaglandins
A
- Uterus important site of prostaglandin synthesis, ↑ synthesis is required for parturition
- Oestrogen induces liberation of PLA2 from lysosomes (labilises lysosomal membranes) & ↑ number of endometrial oxytocin receptors (contractions cannot occur without these)
- Progesterone inhibits release of PLA2 (stabilises lysosomal membranes)
- ↑ oestrogen/progesterone ratio–> ↑ prostaglandin production
14
Q
Regulation of Oxytocin
A
- “Ferguson reflex“- neuroendocrine reflex –>self-sustaining cycle of uterine contractions:
- Fetus causes pressure on the internal end of the cervix –>signals PVN & SON of the hypothalamus–>oxytocin released from P.pituitary stimulates uterine contractions, which in turn ↑ pressure on the cervix–> oxytocin release (positive feedback loop)
- Oxytocin acts to: ↑ myometrial contraction (+ve feedback loop) & ↑ prostaglandin release
15
Q
Onset of Parturition
A
Removal of progesterone–> ↑ in oestrogen: progesterone ratio–> parturition
16
Q
Goat, Cow, Dog, Pig and Rabbit
A
depend on CL to produce progesterone throughout pregnancy
- Goat foetus must stop progesterone production by the CL to start parturition
- The foetal pituitary-adrenal axis determines the timing of onset of parturition
As the foetus grows in a restricted space it becomes stressed–> ↑ in foetal ACTH –>↑ in cortisol–> DHEA (androgen) synthesised & aromatising enzymes released–> ↑ oestrogen production by placenta
- Oestrogen–> ↑ PGF2α –>luteal regression (also causes ↑ contractions & cervical softening)
17
Q
Sheep, Guinea-pig, Cat, (horse)
A
depend on placental progesterone in later pregnancy
- Similar method to above: foetus becomes stressed, foetal ACTH is released & cortisol ↑
- ↑ in foetal cortisol induces 3 enzymes: 17α-hydroxylase, C17-C20 lyase & aromatase- these convert progesterone produced by placenta–> oestrogen therefore ↑ the oestrogen: progesterone ratio
18
Q
Humans
A
- Obtain progesterone from placenta but lacks the enzymes: 17β hydroxylase & C17-C20-lyase ∴ can’t convert progesterone–> oestrogen, can use fetal adrenals to make androgen substrates instead
- Progesterone levels don’t fall at parturition but progesterone receptor complement levels change. ensures that despite the level of progesterone being the same, the progesterone present can’t inhibit myometrial contractions
- PGs act to soften the cervix & ↑ uterine contractions (as in goat and sheep)
19
Q
Mare
A
- Hormone profile in pregnancy is very different to that in other species – no surprise!
- Progestagens ↑ during end stages of gestation whereas total oestrogens ↑ during pregnancy but appear to ↓ before parturition
- Cortisol ↑ only 2-3 days before parturition (in ewe, it is the last few weeks) believed to be the trigger for onset of parturition & other maturational changes (lungs, liver, gut etc)
- PG concentrations= ↓ during pregnancy & ↑ slightly towards term: However, PGFM increases 50-fold during 2-stage of labour.
Progesterone- major hormone only in 1st trimester- from mid gestation, it’s concentration is <1 ng/ml
- Other progestagens increase markedly at this time reaching concentrations between 5-50 ng/ml
- Fetus produces large quantities of pregnenolone–> placenta where its converted into progesterone action of 5α reductase DHP (5α pregnane-3,20-dione)
- DHP= major biologically active progestagen in the mare (binds more avidly than P4 to uterine PRs)
Oestrogens- The ↑ during pregnancy is not down to classical estrogens (estradiol, estriol, estrone)
- Instead, it is due the synthesis of large quantities of equine unique estrogens, equilin & equilenin
(synthesized from farnesyl pyrophosphate)
- Despite this, classical estrogens remain essential for the initiation of labour
20
Q
Ecbolic Drugs
A
**Oxytocin release!**
- PGF2α analogues- (Dinoprost, cloprostenol) –> induce cervical dilation & uterine contractions
- Oxytocin- induces uterine contractions & delivery of placenta
- Used in conjunction with oestradiol benzoate (induces oxytocin receptors)
- Oestradiol inhibits uterine activity but sensitises uterus to oxytocin
Horse: Calcium levels above 40 mg/dl or 200 ppm indicate mare has ↑ probability of foaling in the next 48hours.
Thick waxy exudate accumulates on end of teats 24-48hours prior to foaling
- can give Oxytocin (90min), but not prostaglandins (abdominal pain) or corticosteroids
Cow:
-can give corticosteroids and after prostaglandins
Pig:
-can give prostaglandin with oxytocin following
Sheep:
-corticosteroids
Dog/cat:
can give oxytocin (+anti-progestin)
