Uterine Motility

Question 1

Perimetrium (serosa)

Answer 1

Single thin outer layer of epithelium

Question 2

Myometrium

Answer 2

Thick middle layer of smooth muscle

Question 3

Endometrium

Answer 3

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

Question 4

Uterine Motility

Answer 4

• Uterine contractions depend on gap junctions for phasic propagation of depolarisation. - Connexin 43.
• Hormonally influenced by menstrual cycle, pregnancy, labour.
• Minimal influence of autonomic innervation on contractions under physiological conditions.

Question 5

Gap Junctions

Answer 5

• Membrane proteins form a tunnel between cells (called connexons).
• Allows cells to communicate with each other, share nutrients and transfer chemical/electrical signals.
• Each cell forms half a gap junction and two halves must match in order to form a junction.
• Found in cell/tissue that spread action potential - cardiac muscles, uterine smooth muscle, and nervous tissue in the brain.

Question 6

Connexin Structure

Answer 6

Gap junctions are made of proteins called connexins. Each cell has 6 connexins that form a hemi-channel. Each hemi-channel is specific to another hemi-channel that it will connect to.

Question 7

Uterine smooth muscle

Answer 7

• Inducible especially hormonally
• Fundal dominance during labour
• May arise from anatomical arrangement of expressed gap junctions.

Question 8

Innervation of uterus

Answer 8

• Innervates vascular smooth muscle and myometrium.
• Sympathetic outflow effect depends on receptor type - a-adrenoreceptors = contraction, b-adrenoreceptors = relaxation. Ratio of sympathetic receptor types influenced by hormonal status.
• Also parasympathetic and sensory.

Question 9

Posterior Pituitary Hormones

Answer 9

• Anti-diuretic hormone/arginine vasopressin - primarily works on kidneys.
• Oxytocin - primarily works on uterine muscles and mammary glands. Oxytocin receptor numbers and effect on uterine contraction are influenced by sex hormone levels. At term: falling placental progesterone with sustained oestrogen levels stimulates prostaglandin biosynthesis which leads to oxytocin receptor expression. Uterine smooth muscle sensitive prior to onset of labour. Stimulates increasingly regular, co-ordinated contractions that travel from the fundus to the cervix (fundal dominance). Uterus relaxes completely between contractions.
• Both are 9 amino acid peptides, 2 amino acids difference. Both stimulate contraction of the uterus.

Question 10

Uterine Stimulants (Oxytotics)

Answer 10

• Induce abortion/miscarriage.
• Induce and accelerate labour.
• Contract the uterus after delivery to control postpartum haemorrhage (PPM).
• Examples: Oxytocin (IV infusion to induce or accelerate labour or IV/IM injection after delivery to control postpartum haemorrhage (PPH)), Ergometrine (found to be component responsible for actions on the uterus; weak antagonist/partial agonist for a-adrenoreceptor; causes sustained powerful uterine contraction; se-n/v, largely obsolete in PPH prophylaxis), E & F Prostaglandins (act on cervical ripening and inducing oxytocin receptors). Syntometrine is a combo of oxytocin and ergometrine for 3rd stage of labour.

Question 11

Uterine Relaxants (Tocolytics)

Answer 11

• Delay or treat preterm labour.
• Facilitate obstetric manoeuvres.
• Counteract (iatrogenic) uterine hyperstimulation.
• Treat menstrual cramps/dysmenorrhoea.
• Examples - B2 agonists (ritodrine, terbutaline, salbutamol; increases cAMP levels in smooth muscle; se - tachycardia, hypertension and hyperglycaemia), Ca2+ channel blockers (Nifedipine (used for preterm labour) and Magnesium sulphate; prevent intracellular Ca2+ increase in smooth muscle), NSAIDs (Indomethacin; inhibit prostaglandin biosynthesis), Oxytocin Receptor Antagonist (Atosiban); Nitrates (nitric oxide and nitroglycerine patch).

Question 12

Synthetic analogues of Prostaglandins

Answer 12

• Dinoprostone - equivalent to PGE2, naturally occurring.
• Carboprost - synthetic analogue of PGF2a
• Gemeprost - synthetic analogue of PGE1
• Misoprostol - synthetic analogue of PGE1 - room temp storage, initially used for treatment and prevention of peptic ulcers, medical abortion is performed using Mifepristone (progesterone receptor antagonist used to sensitise myometrium) then Misoprostol, induces labour, controls PPH secondary to uterine atony (not as effective as IV/IM oxytocin). Oral, vaginal, sublingual or rectal routes of administration.

Question 13

Menstrual Symptoms

Answer 13

• Dysmenorrhoea and menorrhagia may be due to prostaglandins - imbalance of PGE and PGF in endometrium?
• NSAIDs are effective pain relief, unclear whether via central analgesic effect or uterine relaxation. - Ibruprofen, naproxen, mefenamic acid. Reduce blood loss. More effective when combined with antifibrinolytics i.e. tranexamic acid.