FRCA Notes

Physiological Changes in Pregnancy

The curriculum asks succinctly for knowledge of the 'Physiological changes associated with pregnancy'.

Resources

  • The physiological changes of pregnancy are largely due to the hormonal effects of progesterone and oestrogen
  • Progesterone and oestrogen both act as respiratory stimulants, increasing ventilatory drive
  • Progesterone also increases the sensitivty to CO2

Anatomical changes

  • In the upper airways, capillary engorgement and tissue oedema occurs
    • Can lead to vocal changes, nasal obstruction and epistaxis
    • May lead to difficult airway management - 10x greater incidence of failed intubation (1 in 250 vs 1 in 2500)

  • Carina displaced cranially - easier endobronchial intubation
  • Rib flaring increases thoracic cage circumference
  • The gravid uterus displaces the diaphragm superiorly

Mechanical and volume changes

  • Inspiration becomes mostly diaphragmatic as the flared rib cage reduces chest wall movement
  • Compliance changes:
    • Lung compliance is unchanged despite bronchial smooth muscle relaxation
    • Chest wall compliance is reduced due to diaphragmatic elevation
    • Therefore total lung compliance is reduced
  • Dead space increases due to bronchodilation

  • Alveolar ventilation increases by 70%
  • Tidal volume increases by 45%
  • Respiratory rate increases by 10%
  • Overall minute ventilation increases by approximately 50%

  • FRC reduces by 20-30% due to reductions in residual volume
  • Closing capacity can encroach on FRC, leading to V/Q mismatch and hypoxia
  • FEV1 and FEV1:FVC remain unchanged
  • TLC and VC remain unchanged

Blood gases

  • Increased alveolar ventilation leads to a fall in PCO2 to 3.7-4.2kPa
  • There is an associated drop in bicarbonate to 18-21mmol/L
  • The compensation is incomplete and pH rises to approximately 7.50
  • Plasma chloride rises to reduce the strong ion difference

  • PO2 rises due to fall in PCO2
  • Approaching term, there is a 60% rise in VO2 (O2 consumption) and VCO2 (CO2 production)
  • The increase in cardiac output (/DO2) doesn't fully match tissue O2 demand and there is a fall in PO2

Oxyhaemoglobin dissociation curve

  • The effect of lower CO2 should be to shift the curve to the left
  • However due to a 30% rise in 2,3-DPG the curve shifts to the right
  • The P50 increases from 3.5 to 4.0kPa

Pulmonary circulation

  • There is a decrease in PVR by term; therefore pulmonary blood flow increases
  • In a healthy mother, this doesn't lead to increases in pulmonary artery, pulmonary capillary or right ventricular pressure

Cardiac output

  • Cardiac output is increased; approximately 50% higher by the end of the second trimester
  • This is partly due to increased resting heart rate (~25%)
  • The predominant cause for the rise in CO is a rise in stroke volume (~30%)
    • Increased preload due to increased plasma volume
    • Myocardial hypertrophy increases contractility

  • Systolic murmur almost universal by term due to higher contractility (diastolic murmur abnormal)

  • During labour itself
    • Cardiac output increases by a further 45-50%
    • In the 3rd stage (i.e. after birth but before placental delivery) it can increase 80% above third trimester levels
    • Contributing factors include:
      • Uteroplacental autotransfusion
      • Pain/anxiety causing catecholamine release
      • IVC relief in 3rd stage, increasing venous return/preload

ECG Changes

  • Left axis deviation
  • TWI in the lateral leads & lead III
  • Q-waves inferiorly (i.e. in III or aVF)
  • Sinus tachycardia
  • Atrial or ventricular ectopics
  • Flattened ST segments

Systemic Vascular Resistance

  • Decreases during pregnancy to accommodate increased CO, owing to:
    1. The effect of progesterone, oestrogens and prostacyclins, which are vasodilatory
    2. The presence of a low resistance vascular bed (the intervillous space of the placenta)
  • Reduces from 1700 dyn.s/cm5 to 950 - 1000 dyn.s/cm5

Blood pressure and flow

  • Decreases; 8% of mothers have a fall in BP 30-50%
  • Diastolic pressure (-25% at 20/40) decreases to a greater extent than systolic pressure (-8% at 20/40)
  • This leads to an increase in pulse pressure
  • Although blood pressure is maximally reduced at 20 weeks, by term it has often returned to near or at baseline BP

  • Organ blood flow changes:
    • 12% of cardiac output to the placenta
    • Increased flow to skin and kidneys
    • Unchanged flow to liver and brain

Aortocaval compression

  • From 13/40 the gravid uterus can compress the IVC ± aorta and cause reductions in BP
  • The effects are variable depending on the BP, positioning and gestation
  • Peak effects at 38/40 - after this the effect is reduced due to descent of the foetal head
  • Effects exacerbated by sympathetic block

  • Supine hypotension syndrome
    • Occurs when aortocaval compression persists despite being put in the left lateral position
    • Can cause maternal shock, foetal hypoxia and bradycardia

  • Those without symptoms still have compression but have adequate collaterals in the epidural plexus to compensate
  • Uteroplacental circulation is NOT autoregulated; IVC compression can significantly decrease flow

Central venous pressure

  • Remains normal during pregnancy unless there is marked aortocaval compression
  • Rises during delivery to 50cmH2O, but is normal during contractions and post-delivery

  • Progesterone is thermogenic and increases basal temperature
  • This may be further increased by use of an epidural (BJA, 2021)

Epidural and intrathecal spaces

  • Aortocaval compression increases pressure/volume of the epidural venous plexus
  • This reduces the volume of the epidural space - solutions will spread more widely within it
  • The epidural space pressure is positive (usually negative in non-pregnant patient)

  • CSF pressure is raised - to 28cmH2O during contractions and 70cmH2O during 2nd stage
  • No change in CSF constituents or specific gravity

Sympathetic nervous system

  • Increased tone through pregnancy, maximal at term
  • Effect is mostly on venous capacitance of lower limbs to counteract IVC compression
  • Sympathetic block may therefore result in a much large drop in BP than in non-pregnancy patients

Drugs

  • Reduced local anaesthetic drug doses required in epidural/spinal:
    • Increased nerve sensitivity
    • Reduced volume of epidural/subarachnoid spaces
    • Lower PCO2 reduces buffering capacity, so LA remain free bases for longer

  • MAC is reduced by 40% (progesterone)
  • Β-endorphin (endogenous opioids) levels are increased throughout pregnancy, labour and delivery
  • Increased sensitivity to opioids

Thyroid

  • Gland increases in size and vascularity, which may lead to goitre
  • There is increased iodine uptake
  • However there is also an increase in thyroid globulin binding protein
  • Hence free T3/T4 levels remain unchanged and the mother remains euthyroid

Pituitary

  • Increased size
  • Vascular supply is mainly by a low-pressure portal venous system rather than systemic arteries
  • This makes the gland susceptible to low BP (Sheehan's syndrome = ischaemic pituitary due to peripartum haemorrhage)

Adrenal

  • Increased cortisol production 5x
  • Reduced cortisol clearance so increase half-life

Pancreas

  • Increased islet of Langerhans and β-cell numbers
  • Insulin production increases and increased receptor sites
  • However there is increased insulin resistance, to provide higher blood glucose levels to facilitate placental transfer

  • Renal plasma flow increases by 50% and GFR increases to 150ml/min
  • Urea and creatinine therefore decline
  • There is increased clearance of drugs - doses may have to be increased

  • Reduced renal tubular re-absorption; glycosuria and proteinuria may occur
  • RAAS and progesterone cause increase sodium and water retention
  • There is relative conservation of potassium but overall reduced plasma osmolality due to expanding plasma volume

  • Progesterone causes smooth muscle relaxation, which may cause urinary stasis and increased risk of UTI

Gastrointestinal

  • Barrier pressure = lower oesophageal sphincter pressure - intragastric pressure
  • The barrier pressure is reduced in pregnancy:
    • The stomach position is altered, pushing the gastric part of the oesophagus intrathoracically, reducing LOS pressure
    • Progesterone also acts as a relaxant
    • The gravid uterus increases intragastric pressure, further increased in Trendelenburg (and to a lesser extent Lithotomy) positions

  • Heartburn therefore occurs in 80% of pregnancies, can occur before 20/40
  • LOS pressure returns to normal 48hrs post-partum

  • Gastric emptying slows but only during labour and with opioids
  • There is increased gastric secretion and reduced gastric pH
  • At risk of Mendelson's syndrome; chemical pneumonitis secondary to aspiration of acidic gastric contents
  • There is a higher risk of aspiration under GA; RSI required from the start of the 2nd trimester onwards

  • Lower GI motility secondary to progesterone - constipation ensues ± haemorrhoids

Hepatobiliary

  • 3x increase in ALP which is produced by the placenta
  • Reduced plasma protein (and plasma cholinesterase) production by the liver, which may mean prolong the effect of NMBA
  • Progesterone reduces CCK production, leading to biliary stasis and increased risk of gallstone production
  • Hepatic blood flow is increased, increasing drug clearance

Blood volume

  • Total blood volume increases by 40-50%

  • Plasma volume increases by up to 50% at term, to approximately 60ml/kg
    • Due to effects of progesterone/oestrogen on the RAAS
    • Rises a further litre in the 24hrs post-partum, then returns to normal by 6 days post-partum

  • Red blood cell volumes decreases by 8/40 but then returns to normal by 16/40
    • By term has increased 30% due to the effects of EPO
  • As RBC volume increases to a lesser extent than plasma volume, there is a dilutional decrease in haematocrit and Hb (Hb ∽110g/L)

  • WCC increases to 14x109 (polymorphs)

Coagulation

  • There is an overall emphasis on increased clotting
    • Increased platelet turnover, clotting and fibrinolysis
    • Increased VTE risk
  • As platelet count remains unchanged, there is an increased production to account for the increased consumption
  • Reduction in bleeding time, PT and APTT due to increased fibrinolysis
Increased Unchanged Decreased
Factor 1 Factor 2 Factor 11
Factor 7 Factor 5 Factor 13
Factor 8 Platelet count Antithrombin III
Factor 9
Factor 10
Factor 12
Plasminogen
Fibrin degradation products

Plasma proteins

  • Reduced albumin and alpha-1-glycoprotein
  • Increased globulins and fibrinogen
  • Total protein drops to 65-70g/L

  • This causes:
    • Reduced plasma oncotic pressure
    • Altered protein binding of drugs e.g. higher toxicity from bupivacaine due to reduced albumin binding
    • Higher ESR and plasma viscosity
    • Reduced plasma pseudocholinesterase activity by 25%

  • Placenta produces the hormone relaxin, which causes ligamentous relaxation
    • Effects include joint laxity and widened symphysis pubis
  • The gravid uterus causes exacerbation of the lumbar lordosis and lower back pain
  • Hyperpigmentation due to increased melanocyte stimulating hormone (MSH) production (face, neck, abdominal midline - linea nigra)

  • 10-20kg weight gain due to increased:
    • Body water and fat
    • Placenta and foetus
    • Amniotic fluid
    • Uterine and breast enlargement

Absorption

  • Reduced gastric emptying in labour can reduce PO bioavailability
  • Delayed gastric emptying leads to increased absorption of drugs from stomach, reduced absorption from intestines
  • May be increased first pass metabolism due to higher hepatic clearance

Distribution

  • Higher TBW, plasma volume and body fat - increases volume of distribution
  • Lower albumin and a1-acid glycoprotein = increased free fraction of certain drugs

Metabolism

  • Higher hepatic blood flow = greater clearance of some drugs
  • There may be increased enterohepatic circulation of drugs
  • Acquired pseudocholinesterase deficiency = prolonged effect of suxamethonium
  • Placental enzymes may metabolise certain drugs/endogenous compounds e.g. placental lactogen degrades insulin

Elimination

  • Greater GFR = higher clearance of some drugs