Physiological Changes In Pregnancy

3.8.2.1. Cardiovascular changes in pregnancy

Cardiovascular changes in pregnancy [Ref: PK1:p346-368]

Haemodynamics Heart rate   

Occurs as early as 4 weeks after conception Increases by 17% by end of 1st trimester Increases to 25% at the middle of 3rd trimester

Stroke volume  

Increased by 20-30% Most of the increase occurs in 1st trimester

Total peripheral vascular resistance    

Decreases by 30% at 12th week By 35% by 20th week Due to vasodilation mediated by progesterone, prostaglandins, and downregulation of alpha-adrenergic receptors Also due to placental blood flow, which acts as an AV-shunt * [KB2:p248]

Cardiac output    

Increase progressively throughout pregnancy 40-45% above non-pregnant values at 12th to 28th week Reach peak of 50% during 32-36th week Then decrease slightly to 47% above non-pregnant level at term

NB: According to [KB2:p248], cardiac output increases by 30% only Causes of cardiac output increase  Venodilation  Increased vascular volume * Caused by oestrogen

Blood pressure   

Decreased in mean arterial blood pressure Systolic BP and diastolic BP decrease by 10% ????Stable after 20weeks

Others Central venous pressure and pulmonary capillary wedge pressure --> Unchanged Oncotic pressure falls by 14% --> Predisposition to oedema

Blood flow and volume Blood flow changes    

Uteroplacental blood flow increase to 750mL/min at term * 85% goes to the placenta Renal blood flow increase by 80% in the first trimester Also increased blood flow to skin, breast, and GIT Cerebral and hepatic blood flow unchanged

Aortocaval compression syndrome  

  

Occurs in about 15% of women near term When supine --> Compression of inferior vena cava --> Decreased venous return and cardiac output --> Hypotension, pallor, nausea, and vomiting May develop as early as the 20th week May also be associated with uterine arterial hypotension and reduced uteroplacenta perfusion May be prevented by lying on the left side

Maternal blood volume Near term  Maternal blood volume is increased by 35-40% (about 1000-1500mLs)  Plasma volume increases by 45% * Due to sodium and water retention by oestrogen stimulation of reninangiotensin system.  RBC volume increases by 20% * Due to increased renal erythropoietin synthesis Thus  The increase in RBC volume is relatively less than the increase in plasma volume --> Haematocrit falls to 33% --> Physiologic anaemia of pregnancy NB: According to [KB2:p248], * Blood volume increase by 40-45% * Plasma volume increase by 50%

* RBC volume increase by 30% * Most of the increase occurs in the first 2 trimester

Labour During labour, each uterine contraction squeezes about 300mL of blood into the central maternal circulation During labour, cardiac output:  Increase by 15% during latent phase of labour  Increase by 30% during the active phase  Increase by 45% during the expulsive stage Maternal systolic and diastolic arterial BP increase by 10-20mmHg during uterine contraction

After delivery Cardiac output and BP returns to non-pregnant level by 2 weeks after delivery

Respiratory changes in pregnancy [Ref: PK1:p349-350]

Changes to anatomy Diaphragm 

Diaphragm is displaced upwards by about 4cm * Contraction is NOT marked restricted

Thoracic cage Anteroposterior and transverse diameters increase by 2-3 cm * Due to lower ribs flare out and increase in subcostal angle (from 68 to 103 degrees)  Circumference increase by 5-7cm These changes are due to relaxin * Secreted by corpus luteum * Relaxes ligament attachments of the ribs 

Other changes  

Capillary engorgement throughout respiratory tract --> Vocal cord may be swollen/oedematous According to [AA4:p630] * Difficult intubation in term pregnant women is 1 in 300, compared with 1



in 2200 in non-pregnant population * Tonge and epiglottis also increase enlarged Large airway dilated --> Decreased airway resistance by 35%

Changes to lung volume Significant changes in lung volume occurs from the 20th week

ERV and RV  

ERV and RV gradually decrease 20% less at term (than non-pregnancy level)

Causes of ERV and RV change 1. Elevation of the diaphragm (main cause) 2. Increase in pulmonary blood volume

FRC  

Decreases by 20% at term In supine, FRC is about 70% of that in erect position

Tidal volume 

NB:  

Tidal volume begins to increase in the first trimester --> 40% above non-pregnant level at term In [PK1:p349], both 28% increase and 40% increase in tidal volume were quoted [JN5:p320, KB1:p249] tidal volume increase by 40%

Capacities At term  Inspiratory capacity (IRV) increases 10%  Expiratory capacity (ERV) decreases 20%  Total lung capacity decrease by 5%  Vital capacity unchanged NB: According to [KB2:p248, AA5:p326] * IRV is unchanged

Other changes Compliance Lung compliance unchanged Chest wall compliance decreases --> Total lung compliance decreases by 20%  

NB: 

Cause: elevation of the diaphragm

Minute ventilation   

Minute ventilation starts to increase in early weeks Maximal hyperventilation occurs as early as week 8-10 Minute ventilation increases to 50% above non-pregnant level at term

Component  40% increase in tidal volume  10% increase in respiratory rate NB:  [KB2:p249] RR increase by 15%  [JN5:p320] RR unchanged Cause  Stimulation of the respiratory centres by progesterone  [JN5:p320] Progesterone sensitise central chemoreceptors --> Increase the slope of pCO2/ventilation response curve by 3 fold  [JN5:p320] Hypoxic ventilatory response is also increased by 2 fold Result At term, (with full renal compensation)  pCO2 = 32mmHg  pO2 increase very slightly due to hyperventilation  Lower bicarbonate level (18-21mmol/L)  pH normal  Increase in 2,3 DPG Overall,  Oxygen dissociation curve stays unchanged

Other notes 

[JN5:p320] Posture makes little difference in oxygenation

Oxygen flux According to [KB2:p249],  Cardiac output increase by 30%  Blood oxygen content decrease due to fall in [Hb] Overall,  Oxygen flux at term is about 10% above non-pregnant level

Changes during and after labour During labour 

Uterine contractions increase O2 consumption by 60%



Minute ventilation increases by 70% due to pain --> Hypocapnia --> Transient hypoventilatory period between contractions --> Brief desaturation of O2

After delivery  

FRC and RV returns to normal within 48 hours Tidal volume declines to normal within 5 days



Decreased FRC and higher O2 consumption --> Reduce the O2 reserve Anatomical changes in upper airway --> More difficult endotracheal intubation

Anaesthetic implication 

Endocrine changes in pregnancy [Ref: PK1:p345-346; WG21:p452-p453]

Production of hormones by placenta Peptide hormone Human chorionic gonadotrophin (hCG)

Production By syncytiotrophoblast cells

Structure Made up of alpha and beta subunits * Like pituitary glycoprotein hormones Alpha subunit is the same as the alpha subunit of LH, FSH, and TSH

Function  

Primarily luteinising and luteotropic * Acts on same receptor as LH Very little FSH activity

Thus, Maintains corpus luteal oestrogen and progesterone production in 1st trimester --> Maintains pregnancy until the placenta takes over

Levels hCG level peaks at 10-12 weeks of pregnancy then declines to term

Other notes Detection  Can be detected in blood as early as 6 days after conception  Can be detected in urine as early as 14 days after conception Secretion in other situation  Small amounts of hCG are also secreted by some GIT and other tumours  Foetal liver and kidney also produce small amounts of hCG Human placental lactogen (hPL) aka human chorionic somatomamotropin (hCS)

Production By syncytiotrophoblast cells Amount produced is proportional to the size of the placenta

Structure Very similar to human growth hormone hPL, growth hormone and prolactin may come from a common progenitor hormone [WG21:p453]

Function    

NB: 

Lipolysis Antagonise actions of insulin * i.e. Decrease glucose utilisation K+, nitrogen, and Ca2+ retention May also inhibit maternal growth hormone secretion Lipolysis and glucose-sparing divert glucose to the foetus

Levels hPL level rises throughout the pregnancy and peaks near term

Steroid hormone i.e. Oestrogen and progesterone Placenta produces enough oestrogen and progesterone from maternal and foetal precursors to take over the function of corpus luteum after the 6th week of pregnancy

Other hormones produced by placenta



  

GnRH and inhibins --> Possible paracrine function to regulate hCG secretion * GnRH stimulates and inhibin inhibits Prolactin Alpha subunits of hCG which cannot combine with beta subunit --> Unknown function Endorphin and enkephalin [PK1:p352]

Changes in pituitary hormones Increase in   

Prolactin ACTH (adrenocorticotrophin) MSH (melanocyte-stimulating hormone)

Decrease in  

Growth hormone * Possibly by hPL (which also has growth hormone activity) Gonadotrophin * By increased level of oestrogen and progesterone

Other changes Adrenal hormones All increase * ???? By oestrogen and progesterone [PK1:p346]  Cortisol (both free and total)  Aldosterone * Due to natriuretic effect of progesterone  Renin and angiotensin

Thyroid hormones  Both T3 and T4 synthesis increase However,  Thyroid binding globulin also increase --> Free plasma level of T3 and T4 are unchanged

Parathyroid hormone  

PTH increase due to increased utilisation of free Ca2+ Increase in PTH --> Increase GIT absorption of Ca2+

Prostaglandins  

Prostaglandin A increase 300% during 1st trimester --> Systemic vasodilation Prostaglanding E only increases during 3rd trimester

Corpus luteum    

Fails to regress when fertilisation occurs Enlarges due to hCG Enlarged corpus luteum of pregnancy secretes oestrogen, progesterone, and relaxin Corpus luteum starts to decline after 8 weeks of pregnancy, but persists throughout pregnancy

Metabolic changes in pregnancy [Ref: PK1:p346]

Basal metabolic rate (BMR) BMR increase to 20% above non-pregnant state at 36 weeks Falls slightly to 15% above non-pregnant state baseline at term Oxygen consumption Oxygen consumption increase by 20% at term NB: [JN5:p320] Oxygen consumption increase by 15-30% at term

Carbohydrate metabolism Insulin secretion increase from end of first trimester to 32 weeks, then declines to non-pregnant level at term Impaired glucose tolerance Tissue sensitivity to insulin diminishes Increased level of hPL, free cortisol, oestrogen and progesterone may contribute

Fat metablism Net storage of fat in the first half of pregnancy --> Decreased FFA and glycerol in plasma Mobilisation during second half --> Increased FFA and glycerol in plasma

Amino acid metabolism Maternal plasma level of amino acid falls due to  Gluconeogenesis

Transplacental transfer Loss in urine

 

NB: 

The foetus uses amino acids for protein synthesis and as an energy substrate

Haematological changes in pregnancy [Ref: PK1:p350]

Haematology Plasma volume increases (45%) relatively more than RBC volume increase (20%) Thus,  [Hb] falls to 12-13g/L  Haematocrit falls to 33-35% Also,  WBC count increases to 8 to 9 x 10^6/L * Due to increase in neutrophil and monocytes NB: According to [KB2:p6],  Without iron supplementation --> RBC volume increase by 250mLs (18%)  With iron supplementation --> RBC volume increase by 450mLs (30%)

Coagulation Significant increase in plasma concentration of  Factor 7,8,9,10  Fibrinogen Platelet concentration is unchanged or slightly decreased due to haemodilution NB: According to [AA4:p328],  Factor II, V slightly increased  Factor VII increase 10-fold  Factor VIII increase 2-fold  Factor IX and X increased  Factor XII increase 30-40%  Factor XI and XIII decreased  Plasminogen inhibitor increased  Plasminogen activator reduced  Antithrombin IIIa decreased slightly

Plasma proteins 

Total circulating protein increase during pregnancy

But, 

Concentration of total protein and albumin decrease due to haemodilution

Other proteins  Increase in total globulin * Increase in alpha and beta-globulin * Slight decrease in gamma-globulin  Fibrinogen increases * From 300mg/dL to 450mg/dL at term  Serum pseudocholinesterase activity * Reduced by 20-30% by the end of 1st trimester * Constant until term

Gastrointestinal changes in pregnancy [Ref: PK1:p350-351] Stomach and intestines are displaced upwards Progesterone relaxes smooth muscles and inhibits the contractile response of the GIT to acetylcholine and gastrin

Lower oesophageal sphincter (LOS) LOS becomes incompetent due to  LOS tone progressively decreases  Change in the angle of gastro-oesophageal junction

Stomach Gastric motility is reduced Delayed gastric emptying at 12-14 weeks of gestation Further gastric emptying delay during labour due to pain and anxiety Acid production Gastrin production increases progressively throughout pregnancy * Produced by the placenta Gastric acid production increased during the 3rd trimester

Intestine Reduced plasma concentration of motilin --> Reduced motility of small and large intestines

Gallbladder Reduced release of CCK (due to progesterone) --> Reduced contractility of the gallbladder

Liver Histological changes in liver * Mild fatty changes * Mild glycogen depletion * Lymphocytic infiltration

Others Increase in serum alkaline phosphatase and serum cholesterol

Renal changes in pregnancy [Ref: PK1:p351-352]

Anatomical changes Obstruction of urine flow by gravid uterus or dilated ovarian plexuses --> Progressive dilatation of the renal pelvis, calyces, and ureters from the 2nd or 3rd months of pregnancy

GFR and RPF GFR and RPF increase by 50% during 1st trimester * Due to increased cardiac output * Urea and creatinine falls in the first 2 trimesters

Glycosuria Glycosuria is common Due to  Increased GFR  Slightly reduced proximal tubular reabsorption

Proteinuria Proteinuria is present in 20% May be due to increased renal venous pressure

CNS changes in pregnancy [Ref: PK1:p352]

Endorphin The placenta produces endorphins and enkephalins * May be analgesic during pregnancy

Endorphin production increases significantly in proportion to the frequency and duration of uterine contractions during labour and delivery * Role unclear

Progesterone Progesterone has sedative actions * Increase 10-20 fold in 3rd trimester

Implication MAC of volatile agents is reduced by 30-40% during pregnancy * Partly because of endorphins and progesterone

Epidural and CSF pressure Epidural veins are engorged Epidural pressure are higher than in non-pregnant women * Due to increased abdominal pressure * May increase to 4-10cmH2O in labour, and to 60cmH2O during bearing-down efforts CSF pressure is not changed at rest May increase to 70cmH2O during bearing-down efforts

3.8. Maternal and foetal 1. Changes to CVS at birth

2. Maternal 3. Placental gas exchange foetal circulation

Before birth Umbilical vessels Umbilical vein x 1 Umbilical arteries x 2

Maternal and foetal Uterine Uterine flow = 600mL/min Maternal [Hb] = 120g/L p50 = 26.6mmHg NB: Uterine blood flow = 500-750mL/min 85% of uterine blood flow goes to placenta Foetal capillaries Umbilical flow = 300mL/min Foetal [Hb] = 170g/L p50 = 18-20mmHg

Umbilical artery pO2 = 18mmHg

Umbilical vein pO2 = 28mmHg ===== [KB2:p251] Respiratory parameters: Neonate vs adult Neonate vs adult

Neonat Adult units e Dead space

2.2

2.2

mL/kg

Tidal volume

7

7

mL/kg

Vd/Vt

0.3

0.3

mL/kg

Alveolar ventilation

120140

6070

mL/kg/min

RR

30-40

1015

breath/mi n

I:E

1

1.5

FRC

30

30

Specific compliance

0.05

0.05 /cmH2O

Oxygen consumption

6-7

3-3.5 mL/kg/min

mL/kg

NB: Foetal oxygen consumption at term = 5 mL/kg/min =====

Physiological anaemia of pregnancy [KB2:p6] During pregnancy, Blood volume increase by 40 to 45% by term Plasma volume increase by 50% by term --> Hemodilution --> Physiological anaemia of pregnancy

NB:  

RBC volume increase by 250mL (18%) without iron supplementation RBC volume increase by 450mL (30%) with iron supplementation

3.8.1. Changes to CVS at birth

Changes to CVS that occurs at birth Step 1 - Umbilical cord clamped Loss of umbilical circulation --> Increase in systemic vascular resistance (SVR) Step 2 - First breath First breath causes  Increase in lung volume * Main reason  Increase in PAO2 * Removal of hypoxic pulmonary vasoconstriction --> Both leads to decrease in pulmonary vascular resistance (PVR) * Reduced to about 1/10th Step 3 - Reversal in atrial pressure gradient Increased SVR and venous return to LA --> Increase in LA pressure Decreased PVR and venous return to RA --> Decrease in RA pressure Therefore, Pressure in LA>RA --> Foramen ovale closes Step 4 - Closure of other shunts

Closure of ductus arteriosus   

Mainly due to increase in PaO2 Decreased circulating PGE2 may also contribute Progressive. Complete within 1-2 days

Closure of ductus venosus  

Mechanism UNKNOWN Cessation of blood flow --> Functional closure

Summary 1. 2. 3. 4. 5.

Loss of umbilical circulation Large increase in pulmonary circulation Closure of forman ovale Closure of ductus arteriosus Closure of ductus venosus

3.8.3. Placental gas exchange Placental blood supply = 500-750 mL/min @ term * 85% goes to placenta Blood supply to uterus is by uterine and ovarian arteries --> Arcuate arteries --> Radial arteries (Penetrating the myometrium) --> Spiral arteries, and basal arteries Spiral arteries supply the intervillous space Basal arteries supply the myometrium and decidua Blood in intervillous space bathes the chorionic villi Chorionic villi have 2 layers of cells * Syncytiotrophoblasts (on the maternal side) * Cytotrophoblasts (on the foetal side) Placental blood flow is not autoregulated * Pressure dependent Foetal [Hb] at birth = 17-18g/dL Typical values of pO2 and pCO2 [KB2:p253] Maternal Uterine artery pO2 = 100 mmHg (SatO2 = 98%) pCO2 = 32 mmHg Uterine vein pO2 = 40 mmHg (SatO2 = 75%) pCO2 = ??45 mmHg Foetal Umbilical artery pO2 = 18 mmHg (SatO2 = 45%) pCO2 = 55 mmHg

Umbilical vein pO2 = 28 mmHg (SatO2 = 70%) pCO2 = 40 mmHg Placental oxygen consumption = 10 mL/kg/min = 1 mL/100g/min = 5 mL/min Placental blood flow ~ 600mL/min Umbilical blood flow ~ 300mL/min Surface area for gas exchange = 12 to 16 square meter