The Physiology of Pregnancy

Introduction

Pregnancy is associated with substantial physiological changes. These primarily comprise adaptations that facilitate fetal growth and development as well as providing the woman with the resources required to carry the pregnancy to term and survive the process of labour. The changes are not proportional to the size of the fetus and, by the end of the first trimester, many systems are functioning at levels close to those at term. This chapter outlines the physiological adaptations for each body system as described in the relevant sections that follow.

Respiratory System

Oxygen consumption is increased by around 15% to 20%. The requirement for this is partly maternal—to satisfy the increase in cardiac output, renal function and other metabolic requirements, including respiratory function and breast and uterine development. Around 40% of the increased oxygen requirement is for the feto-placental unit. To supply this increased oxygen requirement, there is an increase in minute ventilation by about 40% above the normal 7 L/min. This increase in ventilation is far greater than the increase in oxygen consumption, effectively providing a safety net.

The increase is predominantly achieved by increasing tidal volume rather than respiratory rate—in other words, the mother breathes more deeply. This is more efficient than increasing the respiratory rate, as there is less dead-space movement (i.e., that air which is outwith the alveoli and hence not involved in gas exchange). Maternal serum carbon dioxide (CO ₂ ) falls, favouring CO ₂ transfer from the fetus to the mother. These changes are probably mediated by progesterone, which gradually increases during the course of a normal pregnancy . Progesterone increases the sensitivity of the respiratory centre to CO ₂ and has a bronchodilator effect on the smooth muscle tone of the airways. Despite hyperventilation and respiratory alkalosis, blood pH remains almost unaltered at slightly alkalotic values (7.40–7.47), mainly due to renal compensation and increased excretion of bicarbonate.

Throughout pregnancy, spirometry remains within normal limits, with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV ₁ ) and peak expiratory flow (PEF) not changing or modestly increasing.

Breathlessness is a common symptom in pregnancy, reported by 70% of healthy pregnant women. Some women report breathlessness from the first trimester of pregnancy. This dyspnoea is perceptual rather than a reflection of inadequate gas exchange and is often worse at rest. In late pregnancy, the gravid uterus may restrict diaphragmatic movement, exacerbating any feelings of breathlessness. Nevertheless, it is important to consider pathological causes of breathlessness, particularly pulmonary thromboembolic disease.

Cardiovascular System

In pregnancy, there is an increase in cardiac output and a decrease in peripheral vascular resistance.

Cardiac output rises by about 40%, from around 3.5 to 6 L/min, from increases predominantly in stroke volume and to a lesser degree in cardiac rate. As with the respiratory system, these changes are disproportionately greater than required. The fall in peripheral vascular resistance mediated by vasodilatation is not quite compensated for by the increased cardiac output. Thus, the overall effect is a slight fall in blood pressure in the second trimester, sometimes by as much as 5 mmHg systolic and 10 mmHg diastolic. The blood pressure may rise slightly to pre-pregnancy levels in the third trimester. The hyperdynamic circulation of pregnancy can often reveal functional flow murmurs (ejection systolic murmur) and sometimes a third heart sound, which are usually of little clinical significance.

This high blood flow maximises the partial pressure of oxygen (PO ₂ ) on the maternal side of the placenta and optimises oxygen transfer to the fetal circulation. The plasma volume expansion and increased cardiac output may also help heat loss by increasing blood flow through the skin, thus compensating for the increased metabolic rate of pregnancy. Peripheral vasodilatation causes a feeling of warmth and a tolerance to cold and may be a factor in the palmar erythema and spider naevi of pregnancy.

Cardiac output may rise by a further 2 L/min in established labour; this results from an increase in heart rate and stroke volume. Following birth, there is a rapid rise in cardiac output due to the relief of the inferior vena cava and uterine contraction, which empties blood into the systemic circulation. Hence, women with cardiovascular compromise are at greater risk of developing pulmonary oedema during the second stage of labour and the immediate postpartum period. Increased cardiac output returns to pre-labour levels within an hour following delivery and over the next 6 weeks gradually returns to the pre-pregnancy state.

Late in pregnancy, the mass of the uterus is liable to press on, and partially occlude, the inferior vena cava. This reduced venous return leads to a reduced cardiac output and may result in hypotension, so-called ‘supine hypotension’. The clinical importance of this is such that women in later pregnancy and in labour should not lie flat. Ideally, a wedge or other device should be employed to allow the woman to lie at a slight tilt. Supine hypotension often results in a sensation of nausea, but even in the absence of this, may be associated with fetal heart rate abnormalities. All women undergoing caesarean section, elective or emergency, should be placed on an operating table capable of a 15-degree lateral tilt.

Normal findings on electrocardiogram (ECG) in pregnancy include:

• Atrial and ventricular ectopics

• Q wave (small) and inverted T wave in lead III

• ST-segment depression and T-wave inversion in the inferior and lateral leads

• Left-axis deviation

Blood, Plasma and Extracellular Fluid Volume

On average, the total red cell mass increases steadily throughout the pregnancy by 25%, from around 1300 to 1700 mL. The circulating plasma volume, however, increases by 40%, from around 2600 to 3700 mL. Because the plasma volume increases disproportionately more than red cell mass, there is a dilutional drop in the haemoglobin concentration and in the haematocrit such that a haemoglobin level of 105 g/L would be considered normal in a healthy pregnant woman in the third trimester.

Plasma colloid osmotic pressure falls in pregnancy. As a result, fluid shifts into the extravascular compartment, causing oedema. Around 80% of pregnant women have some degree of dependent oedema.

Blood Constituents and Anaemia

The typical changes in the full blood count in pregnancy are shown in Table 42.1 . Iron requirements are increased ( Table 42.2 ) to meet the requirements of the larger red cell mass, developing fetus, and placenta. Therefore, the serum ferritin level falls. The fetus gains iron from maternal serum by active transport across the placenta, mostly in weeks 36 to 40. In the absence of iron deficiency, routine supplementation is not recommended. Nevertheless, iron deficiency is not rare, particularly if iron stores are low before pregnancy. A high index of suspicion is required to aid diagnosis, particularly in at-risk populations and among resource-deficient populations. The World Health Organization (WHO) defines anaemia as haemoglobin levels below 110 g/L in the first trimester and below 105 g/L in the second and third trimesters. Oral iron supplementation is recommended for normocytic or microcytic anaemia. Serum ferritin should be checked in women with known haemoglobinopathy prior to starting iron supplementation.

Haemostasis in Pregnancy

Pregnancy is a hypercoagulable state. There is an increase in procoagulants (particularly fibrinogen but also platelets, factor VIII and von Willebrand factor), a reduction in naturally occurring anticoagulants (e.g., protein S and antithrombin) and an acquired activated protein C resistance ( Figs 42.1 and 42.2 ). The overall fibrinolytic activity is impaired in pregnancy, largely due to placental-derived plasminogen activator type 2 (PAI-2), which is present in substantial quantities during pregnancy. Fibrinolytic activity returns to normal within 1 hour of placental delivery, suggesting that inhibition of fibrinolysis is mediated by the placental unit.

The reason for this hypercoagulable state is, presumably, from a developmental point of view, to minimise blood loss during childbirth. However, the disadvantage is the increased risk of thromboembolic disease. Until the advent of blood transfusion, haemorrhage was a much more important cause of maternal mortality than was thromboembolic disease, and it is possible that hypercoagulability offered an evolutionary advantage.

Compared with the changes in coagulation and fibrinolysis, platelet changes are modest. The platelet count falls only slightly, but there is an increase in aggregability, probably attributed to prostaglandin changes ( Fig. 42.3 ).