The cervix

The cervix is predominantly a fibrous organ with only 10% of uterine muscle cells in the substance of the cervix. Eighty percent of the total protein in the non-pregnant state consists of collagen, but by the end of pregnancy the concentration of collagen is reduced to one-third of the amount present in the non-pregnant state. The principal function of the cervix is to retain the conceptus (Fig. 3.2).

The characteristic changes in the cervix during pregnancy are:

The isthmus

The isthmus of the uterus is the junctional zone between the cervix and the body of the uterus. It joins the muscle fibres of the corpus to the dense connective tissue of the cervix both functionally and structurally. By the 28th week of gestation, regular contractions produce some stretching and thinning of the isthmus, resulting in the early formation of the lower uterine segment.

The lower segment is fully formed during labour and is a thin, relatively inert part of the uterus. It contributes little to the expulsive efforts of the uterus and becomes in effect an extension of the birth canal. Because of its relative avascularity and quiescence in the puerperium, it is the site of choice for the incision for a caesarean delivery.

The corpus uteri

The uterus changes throughout pregnancy to meet the needs of the growing fetus both in terms of physical size and in vascular adaptation to supply the nutrients required:

In the non-pregnant uterus, blood supply is almost entirely through the uterine arteries, but in pregnancy 20–30% is contributed through the ovarian vessels. A small contribution is made by the superior vesical arteries. The uterine and radial arteries are subject to regulation by the autonomic nervous system and by direct effects from vasodilator and vasoconstrictor humoral agents.

The final vessels delivering blood to the intervillous space (Fig. 3.3) are the 100–150 spiral arterioles. Two or three spiral arterioles arise from each radial artery and each placental cotyledon is provided with one or two. The remodelling of these spiral arteries is very important for successful pregnancy. Cytotrophoblast differentiates into villous or EVT. The latter can differentiate further into invasive EVT, which in turn is interstitial, migrating into the decidua and later differentiating into myometrial giant cells, or endovascular that invade the lumen of the spiral arteries. The intrauterine oxygen tension is very low in the first trimester, stimulating EVT invasion.

In the first 10 weeks of normal pregnancy, EVT invades the decidua and the walls of the spiral arterioles, destroying the smooth muscle in the wall of the vessels, which then become inert channels unresponsive to humoral and neurological control (Fig. 3.4). From 10–16 weeks, a further wave of invasion occurs, extending down the lumen of the decidual portion of the vessel; from 16–24 weeks this invasion extends to involve the myometrial portion of the spiral arterioles. The net effect of these changes is to turn the spiral arterioles into flaccid sinusoidal channels.

Failure of this process, particularly in the myometrial portion of the vessels, means that this portion of the vessels remains sensitive to vasoactive stimuli with a consequent reduction in blood flow. This is a feature of pre-eclampsia and intrauterine growth restriction with or without pre-eclampsia.

The uterus has both afferent and efferent nerve supplies, although it can function normally in a denervated state. The main sensory fibres from the cervix arise from S1 and S2, whereas those from the body of the uterus arise from the dorsal nerve routes on T11 and T12. There is an afferent pathway from the cervix to the hypothalamus so that stretching of the cervix and upper vagina stimulates the release of oxytocin (Ferguson’s reflex). The cervical and uterine vessels are well supplied by adrenergic nerves, whereas cholinergic nerves are confined to the blood vessels of the cervix.

Uterine contractility

The continuation of successful pregnancy depends on the fact that the myometrium remains quiescent until the fetus is mature and capable of sustaining extrauterine life. Pregnant myometrium has a much greater compliance than non-pregnant myometrium in response to distension. Thus, although the uterus becomes distended by the growing conceptus, intrauterine pressure does not increase, although the uterus does maintain the capacity to develop maximal active tension. Progesterone maintains quiescence by increasing the resting membrane potential of the myometrial cells while at the same time impairing the conduction of electrical activity and limiting muscle activity to small clumps of cells. Progesterone antagonists such as mifepristone can induce labour from the first trimester, as can prostaglandin F2_α, which is luteolytic. Other mechanisms include locally generated nitric oxide, probably acting through cyclic guanosine monophosphate (cGMP) or voltage-gated potassium channels, while several relaxatory hormones such as prostacyclin (PGI₂), prostaglandin (PGE₂) and calcitonin gene-related peptide, which act through the G_s receptors, increase in pregnancy.

The development of myometrial activity

The myometrium functions as a syncytium so that contractions can pass through the gap junctions linking the cells and produce coordinated waves of contractions. Uterine activity occurs throughout pregnancy and is measurable as early as 7 weeks gestation, with frequent, low intensity contractions. As the second trimester proceeds, contractions increase in intensity but remain of relatively low frequency. In the third trimester they increase in both frequency and intensity, leading up to the first stage of labour. Contractions during pregnancy are usually painless and are felt as ‘tightenings’ (Braxton Hicks contractions) but may sometimes be sufficiently powerful to produce discomfort. They do not produce cervical dilatation, which occurs with the onset of labour.

In late gestation, the fetus continues to grow, but the uterus stops growing, so tension across the uterine wall increases. This stimulates expression of a variety of gene products such as oxytocin and prostaglandin F2_α receptors, sodium channels and the gap junction protein. Pro-inflammatory cytokine expression also increases. Once labour has begun, the contractions in the late first stage may reach pressures up to 100 mmHg and occur every 2–3 minutes (Fig. 3.5). See Chapter 11 for a discussion of labour and delivery.

Cardiac position and size

As the uterus grows, the diaphragm is pushed upwards and the heart is correspondingly displaced: the apex of the heart is displaced upwards and left laterally, with a deviation of ~15%. Radiologically, the upper left cardiac border is straightened with increased prominence of the pulmonary conus. These changes result in an inverted T wave in lead III and a Q wave in leads III and aVF.

The heart enlarges by 70–80 mL, some 12%, between early and late pregnancy, due to a small increase in wall thickness but predominantly to increased venous filling. The increase in ventricular volume results in dilatation of the valve rings and hence an increase in regurgitant flow velocities. Myocardial contractility is increased during pregnancy, as indicated by shortening of the pre-ejection period, and this is associated with lengthening of the myocardial muscle fibres.

Cardiac output

Non-invasive methods, such as echocardiography, are now available, allowing standardized sequential studies of cardiac output throughout pregnancy.

There is a small rise in heart rate during the luteal phase increasing to 10–15 beats/min by mid-pregnancy; this may be related to the progesterone-driven hyperventilation (see below). There is probably a fall in baroreflex sensitivity as pregnancy progresses and heart rate variability falls. Stroke volume rises a little later in the first trimester than heart rate, increasing from about 64 to 71 mL during pregnancy. Women who have an artificial pacemaker and thus a fixed heart rate compensate well in pregnancy on the basis of increased stroke volume alone.

These two factors push the cardiac output up. Most of the rise in cardiac output occurs in the first 14 weeks of pregnancy, with an increase of 1.5 L from 4.5 to 6.0 L/min. The non-labouring change in cardiac output is 35–40% in a first pregnancy, and ~50% in later pregnancies. Twin pregnancies are associated with a 15% greater increase throughout pregnancy.

Cardiac output can rise by another third (~2 L/min) in labour. The cardiac output remains high for ~24 h postpartum and then gradually declines to non-pregnant levels by ~2 weeks after delivery.

Table 3.1 summarizes the percentage changes in some cardiovascular variables during pregnancy.

Total peripheral resistance

Total peripheral resistance (TPR) is not measured directly, but is calculated from the mean arterial pressure divided by cardiac output. The total peripheral resistance has fallen by 6 weeks gestation, so afterload falls. This is ‘perceived’ as circulatory underfilling, which is thought to be one of the primary stimuli to the mother’s circulatory adaptations. It activates the renin–angiotensin–aldosterone system and allows the necessary expansion of the plasma volume (PV; see below: Renal function). In a normotensive non-pregnant woman the TPR is around 1700 dyn/s/cm; this falls to a nadir of 40–50% by mid-gestation, rising slowly thereafter towards term, reaching 1200–1300 dyn/s/cm in late pregnancy. The fall in systemic TPR is partly associated with the expansion of the vascular space in the uteroplacental bed and the renal vasculature in particular; blood flow to the skin is also greatly increased in pregnancy as a result of vasodilatation.

The vasodilatation that causes the fall in TPR is not due to a withdrawal of sympathetic tone, but is hormonally driven by a major shift in the balance between vasoconstrictor and vasodilator hormones, towards the latter. The vasodilators involved in early gestation include circulating PGI₂