Pregnancy is associated with major physiological changes throughout the body. These are caused both by hormonal factors (influential from conception onwards) and by the mechanical changes due to the enlarging uterus (of increasing significance as pregnancy progresses). It is important to understand the normal physiological changes occurring during pregnancy, in order to predict the risks and effects of analgesic and anaesthetic intervention, and also to anticipate the impact of pregnancy on any coexisting medical condition.
Hormonal changes
Following fertilisation, the corpus luteum in the ovary secretes progesterone, oestrogens and relaxin. The placenta takes over the hormone-producing function of the corpus luteum from 6-8 weeks’ gestation onwards and secretes in addition human chorionic somatomam-motrophin (hCS; previously known as human placental lactogen and chorionic growth hormone-prolactin).
Human chorionic gonadotrophin (hCG) can be measured by radioimmunoassay and detected in the blood 6 days after conception, and in the urine 2-3 weeks after conception. It is therefore a useful early diagnostic test of pregnancy. It is produced by the syncytio-trophoblast, and levels rise rapidly during the first 8 weeks of pregnancy, falling to a plateau thereafter.
Progesterone is responsible for most of the hormonally mediated changes occurring during pregnancy. It causes:
• Smooth muscle relaxation
• Generalised vasodilatation
• Bronchodilatation
• Dilatation within the renal tract
• Sluggish gastrointestinal tract motility and constipation
It is thermogenic, causing an increase in basal temperature during pregnancy. It may be responsible for the nausea and vomiting that are common in early pregnancy. Progesterone is a neurotransmitter and, together with increased endogenous endorphins, is implicated in the elevated pain threshold experienced by pregnant women. It also decreases the minimum alveolar concentration (MAC) of inhalational anaesthetic agents. Progesterone has also been demonstrated to enhance conduction blockade in isolated nerve preparations, and it is therefore thought likely to play a role in the decreased requirement for local anaesthetic agents for neuraxial anaesthesia.
Mechanical changes
The uterine fundus progressively enlarges and becomes palpable abdominally by the beginning of the second trimester, at the level of the umbilicus by 20 weeks’ gestation and the xiphisternum by 36 weeks.
Fetal head engagement in the maternal pelvis at the end of pregnancy reduces the fundal height and may alleviate some symptoms attributable to mechanical factors. In multiple pregnancies, the uterus expands to a greater extent and more rapidly, and therefore the mechanical effects are usually greater.
Following delivery the uterus involutes rapidly, and should not be palpable above the maternal umbilicus. It has usually returned to within the pelvis by 72 hours after delivery.
Cardiovascular and haemodynamic changes
Pregnancy
• Blood volume increases throughout pregnancy secondary to hormone-mediated fluid retention, and reaches approximately 45-50% more than pre-pregnant values by term.
• Cardiac output, heart rate and stroke volume all increase as pregnancy progresses. Cardiac output increases by approximately 40-50% by term, with most of the increase occurring by 20 weeks’ gestation. The increased blood flow is distributed primarily to the uterus, where blood flow increases from approximately 50 ml/minute at 10 weeks’ gestation to 850 ml/minute at term. Approximately 1 litre of blood is contained within the uterus and the maternal side of the placenta.
• There is a propensity for arrhythmias that is caused by hormonal effects, increased sympathetic discharge and the stimulation of stretch-activated cardiac ion channels secondary to increased blood volume and cardiac chamber size. The resulting membrane depolarisation may lead to a shortened refractory period, slowed conduction and a mismatch of depolarisation and refractoriness.
• The electrocardiogram in pregnancy may show sinus tachycardia, ectopic beats, shortening of the PR and uncorrected QT intervals, a Q wave and T wave inversion in the lateral leads or lead III, or left axis deviation.
• Renal blood flow increases by 80% over non-pregnant levels by the middle of the second trimester. Glomerular filtration rate and creatinine clearance increase by 50% during pregnancy.
• Systemic vascular resistance falls (peripheral vasodilatation mediated by progesterone, prostacyclin and oestrogens), and there is a decrease in both systolic and diastolic blood pressures, which reach a nadir during the second trimester and then increase gradually towards term, although remaining lower than pre-pregnancy values.
• Aortocaval compression can occur from the middle of pregnancy onward if the supine position is adopted. This is due to mechanical compression of the aorta and inferior vena cava. Venous return is dependent on the competence of collateral circulation via the azygos and ovarian veins. Studies have demonstrated that uterine blood flow decreases primarily as a result of aortic rather than venous compression (see Chapter 13, Aortocaval compression).
• Central venous and pulmonary arterial pressures are unchanged during normal pregnancy.
Labour and delivery
• Cardiac output increases by 25-50% in labour, with an additional 15-30% increase during contractions. This increase in cardiac output is mediated through increased sympathetic nervous system activity, and is therefore significantly attenuated by epidural analgesia.
• Central venous pressure increases during contractions, partly due to sympathetic activity and partly from the transfer of up to 500 ml of blood from the intervillous space. The latter is unaffected by epidural analgesia, as is the increase in central venous pressure which occurs when the Valsalva manoeuvre is performed during pushing.
• Autotransfusion of around 500 ml of blood (from the placenta) occurs during the third stage. There is a sustained increase in cardiac output and central venous pressure for several hours after delivery secondary to intravascular fluid shifts. These haemodynamic changes may be significant in women with cardiac disease or those with pre-eclampsia.
Respiratory changes
Pregnancy
• Progesterone increases the sensitivity of the respiratory centre to carbon dioxide and also acts as a primary respiratory stimulant. These effects are enhanced by oestrogens, and the combined hormonal effect causes an increase in minute ventilation of 45-50%. A sensation of breathlessness is common and is experienced by up to 70% of pregnant women. Physicians should, however, maintain a high index of suspicion when evaluating breathlessness in pregnancy, especially if it is associated with other clinical features. Persistent breathlessness on lying down is an abnormal sign and must be investigated.
• The partial pressure of carbon dioxide in arterial blood (PaCO2) is re-set to approximately 4 kPa during the first trimester and remains at that level throughout pregnancy. A partially corrected respiratory alkalosis is found in normal pregnant women.
• Oxygen consumption increases progressively during pregnancy to 35% above prepregnancy levels.
• Functional residual capacity (FRC) decreases to 80% of pre-pregnancy values as pregnancy progresses, caused by increased intra-abdominal pressure and upward displacement of the diaphragm by the enlarging uterus. Total lung capacity remains unchanged. FRC remains greater than closing capacity throughout pregnancy while the woman remains in an upright position, but falls when a recumbent position is adopted. It has been estimated that airway closure within normal tidal ventilation may occur in as many as 50% of all supine pregnant women during the second half of pregnancy. Consideration should therefore be given to continuous administration of oxygen to women particularly at risk (e.g. those who are obese, and those with respiratory disease).
Labour and delivery
• Massive hyperventilation occurs during labour (unless there is effective analgesia), with minute ventilation increasing to 3-4 times prelabour values.
• PaCO2 falls to below 2 kPa in some women. This respiratory alkalosis is associated with a metabolic acidosis, since maternal aerobic requirement for oxygen (increased by hyperventilation, hyperdynamic circulation and uterine activity) cannot be met, resulting in a progressive lactic acidosis.
• Effective epidural analgesia abolishes these effects during the first stage of labour but not during the second, when the additional uterine activity and work of pushing produce
a further oxygen demand that cannot be met.
• The increased oxygen consumption and reduced oxygen reserves put pregnant women at a significant risk of hypoxia during periods of apnoea, e.g. at the induction of general anaesthesia.
Gastrointestinal changes
Pregnancy
• Lower oesophageal sphincter pressure is reduced because of the smooth muscle relaxant effect of progesterone.
• Intragastric pressure rises as a mechanical consequence of the enlarging uterus.
• The overall effect of these changes is a decrease in gastro-oesophageal barrier pressure, with a concomitant increase in risk of regurgitation and aspiration of gastric contents.
• 75-85% of pregnant women complain of heartburn during the third trimester, and a significant number will have a demonstrable hiatus hernia.
• Gastric emptying is not delayed during pregnancy.
• There is some evidence that gastric volume is increased, and the pH of the intragastric volume may be lower than in the non-pregnant individual.
• Plasma albumin concentration falls due to physiological haemodilution, thus increasing the unbound fraction of highly protein-bound drugs. This may have implications for dose calculation and serum-level monitoring of drugs such as phenytoin, which should be based on measurement of the free drug concentration.
Labour and delivery
• Gastric emptying is now thought to be normal in labour in most cases. However, opioid administration by any route will delay gastric emptying.
• The risk of pulmonary aspiration of gastric contents means that rapid-sequence induction of general anaesthesia, preceded by measures to reduce the acidity of the gastric contents, is required (see Chapter 59, Aspiration of gastric contents).
• Studies suggest that gastric volume (but not acidity) may remain elevated for 48 hours after delivery.
Haematological changes
Total blood volume increases by approximately 1.5 litres during pregnancy, with plasma volume increasing by 30-50% and red cell mass increasing by 20-30% (thus causing the so- called ‘physiological anaemia’ of pregnancy). The magnitude of the increase is greater in women with multiple pregnancy and greatly reduced in women with pre-eclampsia. Plasma volume changes are maximum by mid-pregnancy, returning to normal by approximately 6 weeks postpartum.
The haemoglobin concentration falls by 10-20 g/l by mid-pregnancy; the red cell indices remain approximately constant apart from a small increase in the mean cell volume, unless women become iron/folate-deficient. Postpartum, the haemoglobin concentration usually takes up to 4-6 weeks to reach pre-pregnancy levels.
The white blood cell count increases, peaking at 10-15 x 109/l around mid-pregnancy and increasing further in labour (to up to 30 x 109/l), returning to normal non-pregnant levels by 6-7 days postpartum. Most of the increase is in neutrophils. (Note that the use of steroids in preterm labour can also increase white cell count.)
The platelet count usually remains within the normal range in pregnancy, although population mean counts are slightly lower, with the lower normal limit usually given as approximately 100-120 x 109/l.
Pregnancy represents a state of hypercoagulability; there is increased hepatic production of coagulation factors, especially fibrinogen (increases by approximately 50%) and factor VIII (approximately doubles), but others also increase (II, X and von Willebrand factor). Resistance to activated protein C also increases. Fibrinolytic inhibitors decrease, as do factor XI and protein S activity.
Musculoskeletal changes
The pregnant woman has increased ligamentous laxity, secondary to increased relaxin release, which may lead to increased joint mobility and instability. This may put the woman at risk of musculoskeletal trauma if she has received epidural analgesia, and this risk is considerably higher if she has received either regional or general anaesthesia, when she is unable to safeguard her position. Care is therefore required when positioning, with special attention being paid to the hips and back. The wedged supine position and the use of lateral tilt are compromises and do not reliably relieve aortocaval compression. Women should be encouraged to remain sitting upright or in the full lateral position whenever possible. Walking and standing in labour should also be encouraged.
Key points
• An understanding of the normal physiological changes of pregnancy is essential when caring for the parturient, both in normal pregnancy and delivery and when pathology occurs.
Further reading
Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Semin Perinatal 2015; 39:512-19.
Jarvis S, Nelson-Piercy C. Common symptoms and signs during pregnancy. Obstet Gynaecol Reprod Med 2014; 24: 245-9.