PHYSIOLOGY

Physiology of pregnancy Learning objectives

Laura Talbot After reading this article, you should be able to:
Kirsty Maclennan C describe the changes to lung volumes during pregnancy at term
C chart and explain the physiological anaemia of pregnancy
C state by how much the cardiac output increases in the third
Abstract trimester and by what mechanisms
During pregnancy, maternal physiology undergoes continual adapta-
tion. These, often interlinked, changes affect all the body systems
and are effected by the hormonal influences of the placenta and me- the increased cardiac output or tricuspid and mitral regurgitant
chanical adaptations required to accommodate the growing fetus. murmurs due to dilatation of these valves.
These expected physiological changes can lead to decompensation As pregnancy progresses, diaphragmatic elevation leads to
in parturients with pre-existing co-morbidities or unmasking of pre- displacement of the heart upwards and to the left. This can result
pregnancy disease. A sound knowledge of the expected maternal in ECG changes including leftward axis deviation and T wave
changes is essential to enable accurate interpretation of physiological inversion in the lateral leads and lead III. These changes do not,
and laboratory parameters and implementation of care plans to reduce in themselves, have clinical significance but may mask further
complications. changes secondary to pathological processes. The increase in
Keywords Obstetrics; physiology; pregnancy heart rate necessary to maintain the increased cardiac output
may present as sinus tachycardia and may predispose to
Royal College of Anaesthetists CPD Matrix: 1A01, 2A09, 2B06 tachyarrhythmias.
Aorto-caval compression by the gravid uterus in the supine
position can lead to profound hypotension. This is widely re-
ported to occur from 20 weeks’ gestation onwards. Compression
of the inferior vena cava produces a reduction in preload and,
Introduction therefore, cardiac output. The resultant increase in sympathetic
tone causes vasoconstriction and diversion of blood flow through
During pregnancy, maternal physiology undergoes continual the vertebral and azygos veins, allowing maintenance of blood
adaptation. These, often interlinked, changes affect all the body pressure. However, this adaptive mechanism is not present in up
systems and are effected by the hormonal influences of the to 10% of parturients and those who have sympathetic blockade
placenta and mechanical adaptations required to accommodate as a result of neuraxial anaesthesia. Regardless of the parturient’s
the growing fetus. Knowledge of these changes is essential for ability to compensate for aorto-caval compression, there can still
safe anaesthetic practice. be significant compromise of utero-placental perfusion. To pre-
vent this, the uterus can be displaced by positioning the partu-
Cardiovascular rient with a left lateral tilt or, if this is not feasible, by manual
Most cardiovascular changes occur early in pregnancy. Vascular displacement of the uterus.
smooth muscle relaxation occurs in response to increased
circulating levels of progesterone, oestrogen and prostaglandins, Respiratory
leading to a reduction in systemic and pulmonary vascular The alterations in maternal respiratory physiology occur as a
resistance. Cardiac output gradually increases, eventually by up result of hormonal and biochemical effects on the central respi-
to 30e50% during the third trimester. The increase in cardiac ratory centre, via local effects on the respiratory smooth muscle
output is as a result of an increase in heart rate and stroke vol- or by mechanical effects of the maturing fetus.
ume, secondary to ventricular hypertrophy and increased end Circulating progesterone stimulates the respiratory centre,
diastolic volume. Increases in stroke volume peak at around leading to an increase in minute ventilation, primarily by an in-
weeks 16e24. crease in tidal volume (by w40%) and by an increase in respi-
Blood pressure at term is usually maintained, although there ratory rate (by w15%). The resulting increase in alveolar
may be a transient reduction earlier in pregnancy with a ventilation can produce a decrease in arterial partial pressures of
widening of pulse pressure as diastolic pressure is more signifi- carbon dioxide (PaCO2) and, consequently, a leftward shift of the
cantly affected than systolic. Parturients may also develop mur- oxygen-haemoglobin dissociation curve. However, maternal
murs during pregnancy, these can be flow murmurs as a result of levels of 2,3-DPG also increase throughout pregnancy which
leads to the overall rightward shift in the oxygen dissociation
curve, facilitating oxygen transfer to the fetus. The increased
Laura Talbot BSc (Hons) MB ChB is a Specialty Trainee in the North minute ventilation results in a respiratory alkalosis that is
Western School of Anaesthesia, UK. Conflicts of interest: none partially compensated by increased renal bicarbonate excretion.
declared. Parturients therefore usually have a serum pH at the upper end of
Kirsty Maclennan MBChB MRCP FRCA is a Consultant Obstetric the normal range.
Anaesthetist at St Mary’s Hospital, Manchester, UK. Conflicts of A small increase in PaO2 occurs during the third trimester (to
interest: none declared. w14 kPa), however as the parturient approaches term, the

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 1 Ó 2016 Published by Elsevier Ltd.

Please cite this article in press as: Talbot L, Maclennan K, Physiology of pregnancy, Anaesthesia and intensive care medicine (2016), http://
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 PHYSIOLOGY

increase in chest wall diameter), mucosal oedema, dilation of

Lung volume changes by term small vessels and increased mucosal friability. A more difficult
Lung volume Effect at term compared laryngoscopy view, compounded by rapid desaturation and ur-
to pre-pregnancy gency of the surgery results in a challenging environment.
The importance of optimum pre-oxygenation and positioning
Expiratory reserve volume Decrease 20e30% is essential prior to embarking on general anaesthesia.
Functional residual capacity Decrease 20% The concomitant increase in minute volume and decrease in
Tidal volume Increase 30e40% FRC, speeds up the ‘wash-in’ of volatile anaesthetic agents.
Residual volume Decrease 20% Adequate alveolar concentrations are therefore achieved more
Vital capacity (VC)/Forced expiratory Unchanged quickly on institution of inhalational anaesthesia.
volume in 1 second (FEV1) The balance between bronchodilatation (effected by prosta-
glandin E2 and progesterone) and bronchoconstriction (effected
Table 1 by PFG2a, decreased RV and decreased PaCO2) determines
airway resistance.
increase in cardiac output is unable to keep up with the increased
Diffusing capacity may increase in early pregnancy although
oxygen demands of the gravid uterus and fetus, and the PaO2
this is not clinically significant.
falls (to <13.5 kPa). By term there is a 60% increase in CO2
production and oxygen consumption.
Haematological
During labour there is a further increase in respiratory rate
which results in an acute fall in PaCO2. This increases the affinity The peripartum period sees widespread adaptations in the hae-
of maternal haemoglobin for oxygen and, combined with an in- matological system with a marked increase in risks including
crease in metabolic rate and oxygen consumption, can compro- anaemia, thromboembolism and consumptive coagulopathies
mise oxygen delivery to the fetus. (Table 2).
Expected changes to lung volumes at end term are shown in Increased secretion of aldosterone (by activation of the renin
Table 1. eangiotensin axis) results in an increase in total body water and,
The presence of the gravid uterus can have a ‘splinting effect’ consequently, plasma volume. Erythropoiesis also increases by
on the diaphragm. This is initially compensated for by increases around 30%. These changes are illustrated in Figure 1. The
in the transverse and anterior-posterior diameters of the chest, resulting dilution of red cell mass (physiological anaemia of
facilitated by increased ligamentous laxity which allows flaring pregnancy) is reflected by a reduction in haematocrit.
of the lower rib cage. However, inspiration remains largely a During labour, each contraction ‘squeezes’ blood back into
function of diaphragmatic movement and, by term, functional the circulation. After delivery, approximately 500 ml of blood is
residual capacity (FRC) is reduced by approximately 20%. This, returned into the circulation. While most parturients tolerate this
combined with greater oxygen consumption, renders parturients without adverse effect, it can contribute to decompensation in
more prone to desaturation during induction of general anaes- those with existing cardiac disease. Plasma volume has been
thesia. Airway management in obstetrics can also be more demonstrated to revert to that of pre-pregnancy within 6 days of
complex due to anatomical issues (enlarged breasts and an delivery.

Alterations in the haematological system at term pregnancy

Increased Unchanged Decreased

Blood volume 30e45% Mean corpuscular haemoglobin concentration Haematocrit 35e45%

Plasma volume 45% Lymphocyte/T-cell (although function reduced) Plasma protein 10e14%
Red cell mass 33% Bleeding time Plasma oncotic pressure (haemodilution)
White cell count 8% Antithrombin III
Clotting factors (I, VII, VIII, X, XII, prekallikrein, Platelets
von Willebrand factor, thrombin
Activated partial thromboplastin time,
prothrombin time
Fibrinogen levels 50e80%
Renal erythropoietin/Reticulocyte count
RBC 2,3-diphosphoglycerate (rightward shift in
oxygen-haemoglobin dissociation curve)
Serum albumin concentration
Venous hydrostatic pressure
Erythrocyte sedimentation ratio
Serum lipids 40e60%

Table 2

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Please cite this article in press as: Talbot L, Maclennan K, Physiology of pregnancy, Anaesthesia and intensive care medicine (2016), http://
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 PHYSIOLOGY

Relative changes in red cell, plasma and total blood volumes during
pregnancy (values approximate)

Red cell volume Plasma volume Blood volume

40
% Change from pre-pregnancy

30

20

10

0
0 10 20 30 40 6 weeks
postpartum
Gestation

Figure 1

All clotting factors excluding factors XI and XIII increase Relaxation of ureteric smooth muscle can lead to urinary
throughout pregnancy with a corresponding decrease in throm- stasis. This, combined with external obstructive pressure from
bolytic factors including antithrombin III. Although protective the fetus, confers an increased propensity to urinary tract infec-
against postpartum hemorrhage, it confers a greater risk of tion during pregnancy.
thromboembolic complications. Parturients with pre-existing The increase in plasma volume will increase the volume of
procoagulant pathologies require careful management with distribution of some drugs (particularly those which are more
appropriately dosed low-molecular-weight heparin (LMWH). highly water-soluble, such as thiopentone) e this may have an
The risk of thromboembolic complications is highest within the impact on their eventual clearance.
first 6 weeks postpartum.
The platelet count decreases in pregnancy, as a result of con- Neurological
sumption and the increased plasma volume although production
The nervous system exhibits increased sensitivity to both general
actually increases. Platelet counts are usually maintained within the
and local anaesthetic agents. The minimum alveolar concentratio
normal laboratory reference range. Function is usually preserved.
(MAC) value of several volatile anaesthetic agents has been
The white cell count also increases during pregnancy and,
demonstrated to decrease during pregnancy. The MAC value of
more significantly, in labour. This is primarily due to an increase
sevoflurane is reported to decrease by approximately 30%.
in the neutrophil count and is stimulated by oestrogen. This
Although uterine relaxation is an undesired effect when using vol-
physiological neutrophilia can complicate decision-making
atile anaesthetic agents, these concerns must be balanced against
regarding treatment of sepsis and suitability for regional anaes-
the need to provide adequate anaesthesia. The obstetric population
thesia in labour. Immunological function (both B and T lym-
continue to be over-represented in cases of accidental awareness as
phocytes) is suppressed.
evidenced by the results of 5th National Audit Project.
Local anaesthetic agents can cause a more profound and
Renal
prolonged block, independent of the route of administration.
Renal blood flow and, therefore, the glomerular filtration rate are When performing neuraxial anaesthesia, the volume of local
increased by 50% secondary to an increase in cardiac output. anaesthetic required is reduced due to reduction in epidural
Serum urea and creatinine can be 40% lower than prepregnant volume as a result of engorgement of the epidural veins. Risk of
values. extensive cephalad spread is also increased. A suggested dose
Urinary protein and glucose levels are increased as renal ab- reduction of 25e30% is described.
sorption of these molecules (and others such as bicarbonate and Venous engorgement within the epidural space confers an
some electrolytes) is outpaced by the increase in glomerular filtra- increased risk of intravascular injection, particularly during
tion. The increased bicarbonate loss contributes to compensation of contractions, when the venous pressure in the epidural veins
the respiratory alkalosis driven by increased minute ventilation. reaches its peak.

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Please cite this article in press as: Talbot L, Maclennan K, Physiology of pregnancy, Anaesthesia and intensive care medicine (2016), http://
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 PHYSIOLOGY

Summary of physiological changes of pregnancy

Neurological
• ↑ CSF pressure
• Engorgement of epidural veins
• ↓ MAC
• ↓ LA volumes required Cardiac
• ↑ CO
• ↑ SV
• ↑ HR
• Left ventricular hypertrophy
• Regurgitant murmurs
• ↓ SVR
Respiratory
• ↑ MV (↑ TV and ↑ RR)
• ↓ PaCO2
• ↑ PaO2
• ↓ FRC
Gastrointestinal
• ↓ Lower oesophageal sphincter tone

• ↑ Risk of aspiration
• Liver enzymes (AST, ALT, GGT) ↓
• ↑ ALP

Renal
• ↑
• ↑ GFR
• ↓ Plasma urea and creatinine
• ↑ Urinary protein and glucose
• ↑ Risk of UTI

Musculoskeletal
• ↑ Ligamentous laxity Endocrine
• ↑ Risk of dislocation • ↑ Progesterone and oestrogen
• ↑ Lumbar lordosis • Placenta secretes relaxin, human placental
lactogen and human chorionic gonadotrophin
• Thyroid hyperplasia
• Transient hyperthyroidism
• Insulin resistance
• ↑ Cortisol secretion by adrenal glands

ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CO, cardiac output; CSF, cerebrospinal fluid; FRC, functional
residual capacity; GFR, glomerular filtration rate; GGT, γ-glutamyl transferase; HR, heart rate; LA, local anaesthetic; MAC, minimum alveolar
concentration; MV, minute volume; SV, stroke volume; SVR, systemic vascular resistance; UTI, urinary tract infection.

Figure 2

Gastrointestinal aspiration is thought to revert to that of pre-pregnancy within 24

e48 hours post-delivery.
Lower oesophageal sphincter smooth muscle relaxation and up-
Muscular relaxation also occurs within the gallbladder during
ward displacement of the stomach by the gravid uterus
pregnancy, leading to biliary stasis and increased risk of gallstone
contribute to the increased incidence of reflux during pregnancy.
formation. Plasma levels of most hepatic enzymes (specifically
Although gastric transit is unaffected, there remains an increased
g-glutamyl transferase the transaminases (alanine transaminase
risk of aspiration. Fear, pain and analgesics in labour can com-
(ALT) and aspartate transaminase (AST)) and bilirubin) typically
pound gastric stasis further increasing this risk. The risk of

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Please cite this article in press as: Talbot L, Maclennan K, Physiology of pregnancy, Anaesthesia and intensive care medicine (2016), http://
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 PHYSIOLOGY

decrease during pregnancy, and alternative laboratory ranges Musculoskeletal

have been suggested for obstetric patients. Spider naevi may
Gestational weight gain, with a change in posture required to
occur without clinically significant liver disease.
accommodate the growing fetus, alters the loading pattern on
The placenta produces additional alkaline phosphatase (ALP)
joints and other musculoskeletal structures. For example, lumbar
causing the serum level to rise. Plasma cholinesterase levels
lordosis becomes increasingly exaggerated as pregnancy pro-
decline from the 10th week of pregnancy onwards, reaching a
gresses. In some parturients, these changes can cause significant
nadir in the days following delivery. As most parturients have
pain.
enough functional plasma cholinesterase, the duration of action
The hormones relaxin and oestrogen contribute to increased
of suxamethonium is rarely affected. However, those parturients
ligamentous laxity, particularly in the pelvis. This enables the
with an unrecognized abnormal copy of the gene encoding
fetus to be accommodated but can contribute to musculoskeletal
plasma cholinesterase maybe have an increased duration of
pain during pregnancy. Parturients predisposed to joint insta-
neuromuscular block.
bility have an increased risk of subluxation or dislocation. It is
Plasma protein production decreases and this may have an
important to take particular care when positioning these at-risk
effect on the free concentrations of drugs which are usually
parturients following neuraxial anaesthesia.
highly protein bound.
Conclusion
Endocrine
The adaptive changes that occur in pregnancy affect all of the
Many of the physiological adaptations of pregnancy are due to
body’s systems and are summarized in Figure 2. Knowledge of
increased circulating reproductive hormones including oestrogen
the expected physiological changes is essential to enable
and progesterone. Additionally, the placenta secretes hormones
recognition of pathology, anticipation of possible complica-
such as relaxin, human placental lactogen (HPL) and human
tions and modification of anaesthesia to ensure safe obstetric
chorionic gonadotrophin which contribute to changes within
practice. A
several body systems.
The thyroid gland undergoes follicular hyperplasia and
increases in size. Thyroid stimulating hormone (TSH) receptors FURTHER READING
can be stimulated by B-HCG (as this shares a structural Chan MT, Gin T. Pregnancy potentiates the sedative effects of sevo-
similarity with TSH) which then leads to a transient flurane. Anaesthesiol 2008; 109: A616.
hyperthyroidism. Kamel H, Navi BB, Sriram N, et al. Risk of a thrombotic event after the
Insulin resistance, secondary to placental secretion of HPL, 6-week postpartum period. New Engl J Med 2014; 370: 1307e15.
can result in gestational diabetes. While glucose readily crosses MacLennan K, O’Brien K, Macnab W. Core topics in obstetric
the placenta, insulin does not and the fetus must produce its anaesthesia. Cambridge University Press, 2015.
own. As a result, babies of diabetic mothers tend to have higher Pandit JJ, Andrade J, Bogod D, et al. 5th National Audit Project (NAP5)
birth weights (macrosomia) and may develop hypoglycaemia on accidental awareness during general anaesthesia: summary of
after delivery. main findings and risk factors. Br J Anaesth 2014; 113: 549e59.
Secretion of corticosteroid hormones by the zona fasciculata Peck TM, Arias F. Haematologic changes associated with pregnancy.
of the adrenal gland is increased. The resulting increase in Clin Obstet Gynecol 1979; 22: 788.
cortisol can further contribute to the development of insulin Walker I, Chappell LC, Williamson C. Abnormal liver function tests in
resistance and can also produce changes in skin pigmentation. pregnancy. Br Med J 2013; 347: f6055.

ANAESTHESIA AND INTENSIVE CARE MEDICINE --:- 5 Ó 2016 Published by Elsevier Ltd.

Please cite this article in press as: Talbot L, Maclennan K, Physiology of pregnancy, Anaesthesia and intensive care medicine (2016), http://
dx.doi.org/10.1016/j.mpaic.2016.04.010