Physiological changes of normal pregnancy
Cardiovascular
- dec systemic vascular resistance (~30%) - the primary event, from ~6 weeks
- inc cardiac output 30-50% (inc stroke volume early, inc HR 10-20 bpm later)
- inc plasma volume 40-50%, inc red cell mass 20-30%
- BP falls, nadir at ~20-24 weeks (mid-second trimester), returns to baseline by term
- Aortocaval compression from ~20 weeks -> supine hypotension; left lateral tilt
Haematological
- Dilutional anaemia - plasma volume rises more than red cell mass
- Physiological hypercoagulability - inc factors VII, VIII, IX, X, XII, fibrinogen, vWF; dec protein S; inc PAI-1/PAI-2; dec fibrinolysis
- Mild thrombocytopenia (gestational, ~8-10%), usually >100
- Physiological leucocytosis (neutrophilia), rising further in labour
Respiratory
- Progesterone-driven hyperventilation -> inc tidal volume ~40% (respiratory rate barely changes)
- -> inc minute ventilation ~50% -> compensated respiratory alkalosis
- dec functional residual capacity ~20% (diaphragm elevated), inc O2 consumption ~20-30%
- -> rapid desaturation on apnoea - critical for airway management
- Vital capacity and FEV1 unchanged
Renal
- inc renal plasma flow ~60-80%, inc GFR ~50% (peaks ~mid-pregnancy)
- -> dec creatinine, dec urea, dec urate (urate rises again in the third trimester)
- Physiological glycosuria (lowered tubular threshold); mild proteinuria up to 300 mg/24 h
- Physiological hydronephrosis, R>L - progesterone + mechanical
Endocrine and metabolic
- Progressive insulin resistance from the second trimester (hPL, placental GH, cortisol)
- inc TBG -> inc total T4/T3 with normal free hormone; hCG stimulates the TSH receptor -> TSH falls in the first trimester
- inc cortisol (total and free), inc aldosterone and renin, inc prolactin
- inc calcitriol and intestinal calcium absorption; total calcium falls with albumin, ionised calcium unchanged
Gastrointestinal and hepatic
- dec lower oesophageal sphincter tone -> reflux; delayed gastric emptying
- dec gut motility -> constipation; gallbladder stasis -> stones
- dec albumin; inc ALP (placental) 2-4x; ALT, AST, GGT and bilirubin UNCHANGED
Other
- inc tidal skin pigmentation (melasma, linea nigra), spider naevi, palmar erythema
- Ligamentous laxity (relaxin), lumbar lordosis
- Immune shift toward Th2 - rheumatoid arthritis often improves, SLE may flare
When each change happens - the timing is examinable
| Change | Timing |
|---|---|
| dec SVR, inc CO | From 6 weeks, plateau by mid-second trimester |
| BP nadir | ~20-24 weeks, back to baseline by term |
| Plasma volume peak | ~32 weeks |
| GFR peak | ~mid-pregnancy, then slight decline |
| TSH nadir | First trimester (hCG peak ~10 weeks) |
| Insulin resistance | Progressive from 20 weeks |
| Aortocaval compression | From ~20 weeks |
| Return to baseline | Mostly by 6-12 weeks postpartum; hypercoagulability persists ~6-12 weeks |
Hormonal drivers
- Progesterone
- Smooth muscle relaxation -> dec SVR, dec LOS tone, dec gut and ureteric motility, venous distension
- Direct stimulation of the medullary respiratory centre -> hyperventilation
- Oestrogen
- inc hepatic synthesis of binding proteins (TBG, CBG, SHBG), clotting factors, angiotensinogen
- -> inc renin-angiotensin-aldosterone -> Na and water retention
- hCG - structural homology with TSH -> weak thyrotropic effect -> dec TSH in the first trimester
- Relaxin - vasodilatation, renal vasodilatation, ligamentous laxity
- Human placental lactogen and placental growth hormone - lipolysis, insulin resistance -> spares glucose for the fetus
- Mechanical - gravid uterus -> diaphragm elevation, IVC compression, ureteric obstruction
- Evolutionary logic worth holding: deliver oxygen and glucose to the fetus, expand volume to survive the blood loss of delivery, and be hypercoagulable for the same reason - the same adaptations create the pathology of pregnancy (VTE, gestational diabetes, anaemia)
Reference ranges that change - the highest-yield table
| Test | Pregnancy | Trap |
|---|---|---|
| Haemoglobin | dec (anaemia if <110 g/L first/third, <105 second trimester) | Dilutional, but still investigate iron studies |
| Platelets | Mild dec | <100 is not physiological - think pre-eclampsia, ITP, TTP |
| WCC | inc (up to ~15, higher in labour) | Not evidence of infection |
| Creatinine | dec (~35-70 micromol/L) | *A "normal" creatinine of 90 is renal impairment in pregnancy* |
| Urea, urate | dec | Urate rises in third trimester and with pre-eclampsia |
| Albumin | dec | Falsely lowers total calcium and total thyroid hormones |
| ALP | inc 2-4x (placental) | Not a marker of liver disease |
| ALT, AST, GGT, bilirubin | UNCHANGED | *Any rise is pathological* |
| TSH | dec in first trimester; trimester-specific ranges | Do not diagnose hyperthyroidism on a low first-trimester TSH alone |
| Free T4 | Slight dec late; total T4/T3 inc | Use free hormone with trimester-specific ranges |
| D-dimer | inc progressively | *Useless for excluding VTE in pregnancy* |
| Fibrinogen | inc (up to 6 g/L) | A "normal" fibrinogen in PPH may indicate consumption |
| ABG | pH 7.40-7.47, pCO2 28-32 mmHg, HCO3 18-22 | *A "normal" pCO2 of 40 means impending respiratory failure* |
| BNP | Mildly inc | |
| ESR | inc markedly | Uninterpretable |
| Cholesterol/triglycerides | inc | Physiological |
Normal findings mistaken for disease
- Ejection systolic murmur (>90%), loud S1, S3, bounding pulse, mild peripheral oedema
- Dyspnoea of pregnancy - in ~70%, begins first/second trimester, not exertional, not orthopnoeic
- ECG: left axis shift, small Q and inverted T in III, sinus tachycardia, ectopics
- Chest X-ray: increased cardiothoracic ratio, prominent vascular markings
- Echo: mild four-chamber dilatation, small pericardial effusion, physiological regurgitation
- Pathological until proven otherwise: diastolic murmur, S4, clubbing, fixed splitting, orthopnoea/PND, haemoptysis, raised JVP**
Resuscitation and the acutely unwell pregnant woman
What the physiology changes about clinical decisions.
- Left lateral tilt or manual uterine displacement beyond 20 weeks - aortocaval compression halves cardiac output supine
- dec FRC + inc O2 consumption -> desaturation within 1-2 minutes of apnoea - pre-oxygenate thoroughly; anticipate a difficult airway (oedematous, friable, smaller tube)
- inc aspiration risk - dec LOS tone, delayed emptying -> rapid sequence induction
- Perimortem caesarean section within 4-5 minutes of maternal cardiac arrest >20 weeks - for maternal resuscitation, not only the fetus
- Physiological reserve masks haemorrhage - a young pregnant woman maintains BP until she has lost ~1.5 L; tachycardia and narrowing pulse pressure are the early signs
Interpreting investigations
- Use pregnancy-specific reference ranges - most laboratory "normal" ranges are not
- Do not use D-dimer to exclude PE; go to imaging (CTPA or V/Q - both are acceptable; fetal radiation dose from either is well below the threshold for harm)
- ECG and echo findings above are usually normal variants
Prescribing
- inc volume of distribution, inc GFR, inc hepatic metabolism -> many drugs need higher or more frequent dosing (LMWH, antiepileptics, lithium, digoxin, penicillins)
- dec albumin -> inc free fraction of highly protein-bound drugs (phenytoin - measure free levels)
- Monitor levels where available; anticipate a fall in requirement immediately postpartum
Routine care built on the physiology
- Iron and folate requirements rise; screen for anaemia
- VTE risk is 4-5x, and highest in the first 6 weeks postpartum - assess risk at booking, on admission and postpartum
- Antenatal BP measurement in the correct position with the correct cuff
- Gestational diabetes screening at 24-28 weeks - times the peak of insulin resistance
When physiology becomes pathology
- Physiological changes become the pathology: dilutional anaemia -> iron deficiency anaemia; hypercoagulability -> VTE (4-5x, highest postpartum); insulin resistance -> gestational diabetes; dec SVR -> unmasking of fixed-output cardiac lesions
- Reflux, constipation, haemorrhoids, varicose veins, carpal tunnel syndrome, back pain - all direct consequences
- Gallstones (biliary stasis), urinary tract infection and pyelonephritis (stasis, hydronephrosis)
- Supine hypotensive syndrome
- Melasma, striae, telogen effluvium postpartum
- Cardiac lesions that decompensate with the volume load - mitral stenosis, severe aortic stenosis, pulmonary hypertension, cardiomyopathy
- Renal disease - a mother with pre-existing CKD may not achieve the normal GFR rise
Postpartum
- Most changes reverse by 6-12 weeks postpartum
- Immediately after delivery: autotransfusion of ~500 mL from the contracting uterus -> the period of greatest cardiac strain is the first 24-48 h postpartum, not labour
- This is when women with structural heart disease decompensate
- Plasma volume and cardiac output normalise over 2-6 weeks
- Hypercoagulability persists for at least 6-12 weeks - VTE risk remains elevated through the puerperium
- GFR returns to baseline by ~6-8 weeks - reassess creatinine before concluding there is renal disease
- Insulin resistance resolves within days - stop GDM medication at delivery
- Thyroid function normalises over months; postpartum thyroiditis in ~5%
- Reference ranges should not be re-interpreted as non-pregnant until ~12 weeks postpartum
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