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MD3002 Week 1 0 > 7. Uterine motility > Flashcards

7. Uterine motility Flashcards

1
Q

What are the 3 layers of the uterine wall?

A

Perimetrium (serosa): Single thin outer layer of epithelium, not evident clinically

Myometrium: Thick middle layer of smooth muscle. 3 layers to produce adequate force for labour.

Endometrium: Inner layer with glands, blood vessels, lymphatics and epithelial cells

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2
Q

What are gap junctions?

A

Gap junctions are a specialized intercellular connection between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells.

Allow the progression from electrical stimuli to mechanical stimuli, allows phasic propagation of depolarisation in uterine smooth muscle.

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3
Q

What are uterine contractions dependent on in their cell wals?

A

Gap junctions for phasic propagation of depolarisation. Requires connexin 43

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4
Q

Hormones from which 3 events influence uterine motility?

A

Menstrual cycle
Pregnancy
Labour

Influences the abundance of gap junctions present. Produces stronger contractions in pregnancy. Hormones are uterus equivalent of the hearts SAN.

Minimal influence of autonomic innervation on contractions under physiological conditions

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5
Q

Intercalated discs

A

Provide structural support to adjacent cells

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6
Q

Connexin structure

A

Sit on top of one another to form connexin 45

Transmembrane proteins.

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7
Q

At which 3 sites in your body are gap junctions found?

A
  1. Cardiac muscle
    - Constitutively expressed, always ON
    - Arranged in intercalated discs
    - Depolarisations starts from the SAN
  2. Vascular/intestinal smooth muscle
    - Constitutively expressed
    - Not concentrated in specialised areas
  3. Uterine smooth muscle
    - Inducible (esp hormones)
    - Fundal dominance during labour may arise from anatomical arrangement of expressed gap junctions.
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8
Q

Connexin 43 expression

A

(From rat specimen)
Immunofluoroescence is absent day 4
Evident day 14
Prominent day 20 (term in rat)

Disappears postnatally.

I.e. more gap junctiosn and more connexins when they are physiologically needed, i.e. end of pregnancy

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9
Q

Innervation of the uterus?

A

• Sympathetic, parasympathetic and sensory.

• Innervation of vascular smooth muscle and
myometrium.

• Sympathetic outflow effect depends on receptor type.

  1. a-adrenoceptors: contraction.
  2. b-adrenoceptors: relaxation.

• Ratio of sympathetic receptor types influenced by hormonal status.

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10
Q

Posterior pituitary hormones?

A
  1. Antidiuretic hormone (ADH)/vasopressin (primarily acts on kidneys)
  2. Oxytocin
    Both 9 amino acid peptides, 2 amino acids different.
  • Both stimulate CONTRACTION of the uterus.
  • Oxytocin receptor numbers are influenced by sex hormone levels.
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11
Q

Oxytocin receptor expression at term?

A

– Falling placental progesterone with sustained oestrogen levels.
–> Stimulates prostaglandin biosynthesis.
–> Oxytocin receptor expression.
-Uterine smooth muscle sensitive prior onset of labour
–>Stimulates increasingly regular, co-ordinated contraction that travel from fundus to the cervix (fundal dominance)

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12
Q

Between contractions the uterine…

A

relaxes completely to allow the uteroplacental circulation to continue

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13
Q

Uterine stimulants, role?

A

I.e. oxytocics

  • Induce abortion
  • Induce and accelerate labour
  • Contract the uterus after delivery to control postpartum haemorrhage (PPH)
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14
Q

Uterine relaxants, role?

A

I.e. Tocolytics (stop, birth)
- (Treats menstrual cramps and dysmenorrhoea)
– Prevent or treat preterm labour.
– Facilitate obstetric manoeuvres.
– Counteract (iatrogenic) uterine hyperstimulation.

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15
Q

Options for administrating uterine stimulants (oxytocics)

A
  1. Oxytocin.
    • IV infusion to induce or accelerate labour.
    • IV or IM injec7on aber delivery to control postpartum
    haemorrhage (PPH).
  2. Ergometrine.
  3. E & F series prostaglandins.
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16
Q 
Ergometrine:
5-HT receptor?
alpha-adrenoreceptor?
Dopamine receptor?
Uterine contraction?
Main uses?
A

5-HT receptor: Antagonist/partial agonist
Alpha-adrenoreceptor: Weak antagonist/partial agonist
Dopamine receptor: Weak
Uterine contraction: +++
Main uses: Obstetric haemorrhage

17
Q

Uses of ergometrine in practice?

A
  • Still useful for bleeding related to early pregnancy complications: E.g. miscarriage (oxytocin is not effective).
  • Causes sustained powerful uterine contractions.
  • Largely obsolete for postpartum haemorrhage (PPH) prophylaxis. Don’t use in the presence of hypertension (due to vasoconstriction), adverse effect of nausea/vomiting.
18
Q

What is syntometrine?

A

• Syntometrine is the combination of oxytocin and ergometrine for the third stage of labour, commonly in use untol 1990s.

19
Q

Prostaglandins role in pregnancy?

A
  • Endometrium/decidua and myometrium = prostaglandin synthesising capacity.
  • Membrane phospholipid substrate in late pregnancy.
  • Prostaglandin F2a (PGF2a) generated in large amounts. Prostaglandin I2/prostacyclin and prostaglandin E2 also occur naturally.
  • F series more vasoconstrictor
  • E series vasodilator,
  • Both E and F act on cervical ripening and induce oxytocin receptors.
20
Q

Name 4 examples of prostaglandin drugs?

A

Dinoprostone: Equivalent to prostaglandin E2, naturally occurring
Carboprost: Synthetic analogue of prostaglandin F2a (PGF2a)
Gemeprost: Synthetic analogue of prostaglandin E1 (PGE1)
Misoprostol: Synthetic analogue of prostaglandin E1 (PGE1)

21
Q

What is misoprostol?
Uses?
Administration?

A

What is misoprostol? PGE1 analogue

Uses:

  • Medical abortion, myometrium sensitised by mifepristone (progesterone receptor antagonist) then misoprostol
  • Induction of labour
  • Control of PPH (postpartum haemorrhage) secondary to uterine atony

Administration: Oral, vaginal, sublingual or rectal routes of administration

22
Q

What are the 5 categories of uterine relaxants (tocolytics)?

A 
b2-agonists
calcium channel blockers
NSAIDs
Oxytocin receptor antagonists
Nitrates
23
Q

How do b2-agonists act as urerine relaxants?
Name 3 examples
Side effects

A

E.g. Ritodrine, terbutaline, sabutamol

MoA:
-Increase cyclic AMP levels in smooth muscle

Side effects: Tachycardia, hypertension and hyperglycaemia

24
Q

Name two examples of Ca channel blockers as uterine relaxants? MoA?

A

E.g. Nifedipine (the current drug choice for preterm labour), Mg sulphate

MoA: Prevent intracellular Ca increase in smooth muscle

25
Q

Which NSAIDs act as a uterine relaxant? Action?

A

Indomethacin

MoA: Inhibits prostaglandin biosynthesis

26
Q

Name an oxytocin receptor antagonist?

A

Atosiban

27
Q

How are nitrates used as uterine relaxants?

A

NO donors

Nitroglycerine patch

28
Q

what is the cause for dysmenorrhoea and menorrhagia?

A

Imbalance of PGE and PGF in endometrium

29
Q

Which NSAIDs are used to treat menstrual symptoms?

A

Ibuprofen
Naproxen
Mefanamic acid

Either via uterine relaxation or central analgesic effect.

MD3002 Week 1 0 (11 decks)

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