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, 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 oe strogen 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, labour, each uterine contraction squeezes about 300mL of blood into the central maternal circulation During labour lab our,, 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 lev el 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 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 Tonge and epiglottis ep iglottis 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 Elevation of the the diaphrag diaphragm m (main (main cause) cause) 2. Increa Increase se in pulmon pulmonary ary bloo blood d volume volume
FRC
Decreases by 20% at term In supine, FRC is about 70% of that in erect position
Tidal volume
Tidal volume begins to increase in the first trimester --> 40% above non-pregnant level at term
NB:
In [PK1:p349], both 28% increase and 40% increase in tidal volume were quoted [JN5:p320, KB1:p249] KB1:p249] tidal volume increase incr ease 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] AA5:p326] * IRV is unchanged
Other changes Compliance Lung compliance unchanged Chest wall compliance decreases --> Total 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 lev el 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 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 l evel (18-21mmol/L) pH normal Increase in 2,3 DPG Overall, Oxygen dissociation curve stays unchanged
Other notes
[JN5:p320] Posture 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 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
Anaesthetic implication
Decreased FRC and higher O2 consumption --> Reduce the O2 reserve Anatomical changes in upper airway --> More difficult endotracheal intubation
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 p rolactin may come from a common progenitor hormone [WG21:p453]
Function
Lipolysis Antagonise actions of insulin * i.e. Decrease glucose utilisation K+, nitrogen, and Ca2+ retention May also inhibit maternal growth hormone secretion
NB:
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 lu teum 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 fre e Ca2+ Increase in PTH --> Increase GIT absorption of Ca2+
Prostaglandins
Prostaglandin Prostaglandin A increase 300% during 1st trimester --> Systemic vasodilation Prostaglanding 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, 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 ener gy 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 decre ased 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 d dilated ilated ovarian plexuses --> Progressive 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 th e 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, 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
7
7
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 3-3.5 mL/kg L/kg//min
Tidal volume
mL mL/kg
mL/kg
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%) (18%) without iron supplementation supple mentation RBC volume increase by 450mL (30%) (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 incre ase 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 Loss of umbili umbilical cal circu circulat lation ion Large increase increase in pulmona pulmonary ry circulat circulation ion Closure Closure of forman forman ovale ovale Closure Closure of duct ductus us arter arterios iosus us Closure Closure of ductus ductus venosu venosuss
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