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Physiological Changes of Pregnancy - System-wise

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Quick Reference: Maximum Changes at Term

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1. Cardiovascular System

• Plasma volume increases by ~55%, red blood cell mass by ~45%, producing dilutional (physiological) anaemia - hemoglobin typically stays >11 g/dL
• Total blood volume increases by 1000-1500 mL at term (~90 mL/kg), allowing tolerance of delivery blood loss (200-500 mL vaginal, 800-1000 mL caesarean)
• Blood viscosity is reduced

• Cardiac output rises by 40% at term (HR up 20% + SV up 30%)
• Increase begins in the first trimester (mainly stroke volume initially), then heart rate contributes progressively
• CO does not appreciably rise further in the third trimester - the greatest surges occur during labour and immediately post-delivery
• Cardiac chambers enlarge; myocardial hypertrophy is visible on echocardiography

• Peripheral vascular resistance falls due to reduced smooth muscle tone (progesterone) and vasodilatory effect of progesterone and prostacyclin
• Nadir of peripheral resistance is mid-second trimester
• Systolic BP falls slightly (-5%), diastolic BP falls more (-15%)
• Pulmonary vascular resistance drops ~30%; pulmonary pressures remain normal despite increased flow
• CVP, PCWP, and PAP remain essentially unchanged

• After week 20, the gravid uterus compresses the inferior vena cava in the supine position, reducing venous return and cardiac output
• ~5-10% develop supine hypotension syndrome (pallor, sweating, nausea, hypotension)
• Uterus also compresses the aorta, reducing uteroplacental perfusion
• Management: left lateral tilt (>15° wedge under right hip)
• Chronic partial IVC compression causes venous stasis, oedema, phlebitis, and varicosities of the lower extremities and haemorrhoids

• Diaphragm elevation shifts the heart leftward - left axis deviation and T-wave changes on ECG
• Chest X-ray shows apparent cardiomegaly
• Systolic ejection murmur (from increased flow) is common and normal
• Uterine blood flow at term: 600-700 mL/min (~10% of CO), vs. 50 mL/min non-pregnant

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2. Respiratory System

• Minute ventilation increases by 50% (predominantly via tidal volume increase of ~40%, with a smaller increase in respiratory rate ~15%)
• Driven by elevated progesterone, which increases sensitivity of respiratory centres to CO2 and acts as a direct respiratory stimulant
• PaCO2 decreases to 28-32 mmHg (mild respiratory alkalosis)
• Compensatory renal bicarbonate excretion prevents frank alkalosis (HCO3- decreases ~15%)
• PaO2 rises slightly (104-108 mmHg at term)
• P50 for hemoglobin shifts right (27 → 30 mmHg) due to elevated 2,3-DPG - offsetting hyperventilation's leftward shift and enhancing O2 delivery to tissues

• FRC decreases by 20% (principally reduction in expiratory reserve volume from larger tidal volumes)
• Vital capacity and closing capacity are minimally affected
• Total lung volume falls ~5% due to diaphragm elevation (up to 4 cm)
• Airway resistance decreases by ~35% (hormonal bronchodilation)
• Flow-volume loops are unaffected

• Diaphragm elevated up to 4 cm; compensated by widening of the chest (anteroposterior diameter increases; lower chest wall widens up to 7 cm)
• Diaphragmatic motion is not restricted
• Respiratory mucosa becomes engorged - predisposing to trauma, bleeding, and obstruction during laryngoscopy; smaller endotracheal tubes (6-6.5 mm) should be used

• Decreased FRC + increased O2 consumption = rapid desaturation during apnea; pre-oxygenation before induction is mandatory
• Closing volume may exceed FRC in some pregnant women, causing small airway collapse in the supine position
• Intrapulmonary shunting increases toward term

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3. Haematological System

• Dilutional anaemia due to disproportionate plasma expansion (55%) over RBC mass increase (45%)
• Haemoglobin typically >11 g/dL; haematocrit falls
• Increased demand predisposes to iron deficiency and folate deficiency anaemia if supplements are not taken
• Rightward shift of O2-Hb dissociation curve (elevated 2,3-DPG)

• Leukocytosis up to 21,000/μL, especially in the third trimester and during labour (mainly neutrophilia)

• Platelet count decreases by ~10% (gestational thrombocytopenia) - usually mild

• Procoagulant factors increase: fibrinogen, factors VII, VIII, IX, X, XII all elevated (by 30-250%)
• Factor XI may decrease
• Antifibrinolytic activity increased
• Accelerated fibrinolysis can be observed in the late third trimester
• Net result: a hypercoagulable state - protective against haemorrhage at delivery but increases VTE risk
• Protein S decreases; APC resistance increases

• Serum albumin decreases (dilutional), reducing colloid oncotic pressure
• Pseudocholinesterase activity decreases 25-30% (relevant for succinylcholine metabolism)
• Fibrinogen and globulins increase
• ESR is elevated (not useful in pregnancy)

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4. Renal System

• Renal plasma flow increases by ~80% by mid-pregnancy
• GFR increases by 50% - the most clinically significant renal change
• Serum creatinine falls to as low as 0.5 mg/dL (normal non-pregnant ~0.8-1.0 mg/dL)
• BUN decreases to as low as 9 mg/dL
• A creatinine of 1.0 mg/dL or BUN of 14 mg/dL that would be "normal" non-pregnant indicates significant renal impairment in pregnancy

• Decreased renal tubular threshold for glucose and amino acids
• Glycosuria (1-10 g/day) is common and physiological - does not indicate diabetes
• Mild proteinuria (<300 mg/day) is acceptable upper limit
• Plasma osmolality decreases by 8-10 mOsm/kg (resetting of osmoreceptors)

• Ureters and renal pelves dilate (more pronounced on the right due to dextrorotation of uterus and right ovarian vein compression) - physiological hydronephrosis
• Increased risk of pyelonephritis from ascending urinary stasis

• Renin, aldosterone, and angiotensin II all increase substantially
• Despite elevated angiotensin II, pregnant women are relatively resistant to its vasopressor effect
• Aldosterone rises to retain sodium and water - expanding ECF volume

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5. Gastrointestinal System

• Elevated progesterone + decreased motilin → smooth muscle relaxation throughout the GI tract
• Gastric tone and motility are reduced
• Lower oesophageal sphincter (LES) tone decreases - combined with elevated intra-abdominal pressure from the gravid uterus → GERD, oesophagitis, and risk of regurgitation
• Gastric acid content and volume do not change significantly, but aspiration risk is greatly increased
• Upward and anterior displacement of the stomach by the uterus worsens LES incompetence
• Gastric emptying is delayed (especially during labour with opioid use) - Mendelson's syndrome risk

• Small bowel transit time increases; nutrient absorption is unchanged except iron absorption increases (due to increased iron requirements)
• Colon: constipation from increased sodium/water absorption, decreased motility, and mechanical obstruction by the uterus

• Hepatic blood flow and overall function are essentially unchanged
• Spider angiomas and palmar erythema from elevated oestrogen
• Hypoalbuminaemia (dilutional)
• Serum alkaline phosphatase mildly elevated (placental isoenzyme)
• Serum cholesterol, fibrinogen elevated
• Serum bilirubin and transaminases remain normal; mild elevations may occur in third trimester
• Pseudocholinesterase activity falls 25-30%
• Colloid oncotic pressure is reduced

• Gallbladder volume may double in second/third trimesters
• Gallbladder emptying is markedly slower (progesterone inhibits cholecystokinin release)
• Bile becomes more lithogenic → increased risk of cholesterol gallstones
• Up to 4% have gallstones on routine obstetric ultrasound; only 1/1000 become symptomatic
• Haemorrhoids develop from increased portal venous pressure and IVC compression

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6. Central Nervous System

• MAC (minimum alveolar concentration) decreases progressively throughout pregnancy, by up to 40% at term for all inhalational agents
• Returns to normal by the 3rd day after delivery
• Driven primarily by elevated progesterone (sedating at pharmacological doses; rises up to 20x normal at term) and β-endorphin surge during labour

• Enhanced sensitivity to local anaesthetics during regional anaesthesia
• Epidural dose requirements reduced by up to 30% (hormonally mediated + epidural vein engorgement)
• Epidural venous engorgement (from IVC compression) causes:
  1. Decreased spinal CSF volume
  2. Decreased potential volume of epidural space
  3. Increased epidural pressure (may be positive rather than negative)
  • Net effect: enhanced cephalad spread of local anaesthetic
  • Also increases risk of inadvertent intravascular injection of epidural catheter

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7. Endocrine and Metabolic System

• Anterior pituitary doubles/triples in size (lactotroph hyperplasia/hypertrophy)
• Pituitary volume increases 40% (2nd trimester), 75% (3rd trimester), up to 120% immediately postpartum
• Prolactin increases ~10-fold by term (oestrogen-stimulated)
• LH and FSH decrease (despite elevated GnRH)
• Placental GH variant progressively replaces pituitary GH in later pregnancy; IGF-1 rises

• Corticosteroid-binding globulin triples → total plasma cortisol elevated, but free cortisol also rises 2-3x (reflected in elevated urinary free cortisol)
• ACTH increases 2-4x (partly from placental ACTH - not suppressible with exogenous steroids)
• CRH rises progressively (placental source), peaking at delivery
• Diurnal variation of cortisol is retained but blunted
• Placental 11-β-HSD2 inactivates cortisol to cortisone, protecting the fetus
• Aldosterone markedly elevated (see Renal section); maintains expanded plasma volume

• hCG (structurally similar to TSH) stimulates thyroid hypertrophy
• Thyroid-binding globulin increases → total T4 and T3 elevated
• Free T4 and T3 remain normal - patient is euthyroid
• TSH transiently decreases in the first trimester (hCG effect)
• Basal metabolic rate increases

• Insulin levels rise steadily throughout pregnancy
• Insulin resistance increases (driven by hPL/human chorionic somatomamotropin, cortisol, progesterone)
• Pancreatic beta-cell hyperplasia occurs to compensate
• Blood glucose and amino acids are lower (diverted to fetus); free fatty acids, ketones, and triglycerides are elevated
• Resembles an accelerated starvation state fasting, with fed-state diabetogenic response
• This is the basis of gestational diabetes in susceptible women

• Secreted by the placenta and endometrium throughout pregnancy
• Softens the cervix, inhibits uterine contractions
• Relaxes pubic symphysis and pelvic joints - contributes to back pain, pubic symphysis diastasis, ligamentous laxity

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8. Musculoskeletal System

• Relaxin causes ligamentous laxity of the spine and pelvic joints - increases risk of back injury
• Centre of gravity shifts anteriorly - lumbar lordosis increases
• Pubic symphysis widens
• Back pain is common (reported in up to 50% of pregnancies)
• Carpal tunnel syndrome may develop from fluid retention
• The diaphragm is elevated and the lower chest wall widens (anteroposterior diameter increases)

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9. Skin and Integumentary System

• Spider angiomas and palmar erythema from elevated oestrogen
• Hyperpigmentation: linea nigra, melasma (chloasma - "mask of pregnancy"), darkening of areolae and genitalia - from elevated MSH and oestrogen
• Striae gravidarum (stretch marks) from skin stretching and altered connective tissue
• Increased skin blood flow and sweating
• Hair changes: anagen phase prolonged during pregnancy → postpartum telogen effluvium (hair loss after delivery)
• Nails may become brittle

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10. Uteroplacental Circulation

• Uterine blood flow increases from ~50 mL/min to 600-700 mL/min at term (~10% of cardiac output)
• 80% of uterine blood flow goes to the placenta
• Uterine vasculature is maximally dilated at term - no autoregulation
• Remains sensitive to α-adrenergic agonists (vasopressors can reduce uteroplacental flow)
• Extreme hypocapnia (PaCO2 <20 mmHg) reduces uterine blood flow and causes fetal hypoxaemia
• Three major factors reducing uterine blood flow: hypotension, uterine contractions, vasoconstrictors

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Summary Table - Key Clinical Implications

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• Morgan and Mikhail's Clinical Anesthesiology, 7e - comprehensive system-wise summary
• Sabiston Textbook of Surgery - surgical and GI/cardiovascular focus
• Creasy & Resnik's Maternal-Fetal Medicine - endocrine, pituitary, and adrenal changes
• Braunwald's Heart Disease - cardiovascular changes