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 down-regulation 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:
Transcript
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 down-regulation 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
OthersCentral 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 volumeNear 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 renin-angiotensin 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
LabourDuring 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 deliveryCardiac 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 volumeSignificant 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 change1. 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 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] tidal volume increase by 40%
CapacitiesAt term
Inspiratory capacity (IRV) increases 10% Expiratory capacity (ERV) decreases 20% Total lung capacity decrease by 5% Vital capacity unchanged
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
ResultAt 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
Other notes [JN5:p320] Posture makes little difference in oxygenation
Oxygen fluxAccording 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
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)
ProductionBy syncytiotrophoblast cells
StructureMade 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
LevelshCG level peaks at 10-12 weeks of pregnancy then declines to term
Other notesDetection
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)
ProductionBy syncytiotrophoblast cells Amount produced is proportional to the size of the placenta
StructureVery similar to human growth hormone hPL, growth hormone and prolactin 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
LevelshPL level rises throughout the pregnancy and peaks near term
Steroid hormonei.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 hormonesAll 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 consumptionOxygen consumption increase by 20% at term NB: [JN5:p320] Oxygen consumption increase by 15-30% at term
Carbohydrate metabolismInsulin secretion increase from end of first trimester to 32 weeks, then
declines to non-pregnant level at term
Impaired glucose toleranceTissue sensitivity to insulin diminishes Increased level of hPL, free cortisol, oestrogen and progesterone may
contribute
Fat metablismNet 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 metabolismMaternal 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]
HaematologyPlasma 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
StomachGastric motility is reduced Delayed gastric emptying at 12-14 weeks of gestation Further gastric emptying delay during labour due to pain and anxiety
Acid productionGastrin production increases progressively throughout pregnancy
* Produced by the placenta Gastric acid production increased during the 3rd trimester
IntestineReduced plasma concentration of motilin
--> Reduced motility of small and large intestines
GallbladderReduced release of CCK (due to progesterone)
OthersIncrease in serum alkaline phosphatase and serum cholesterol
Renal changes in pregnancy[Ref: PK1:p351-352]
Anatomical changesObstruction 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
GlycosuriaGlycosuria is common Due to
Increased GFR Slightly reduced proximal tubular reabsorption
ProteinuriaProteinuria is present in 20% May be due to increased renal venous pressure
CNS changes in pregnancy[Ref: PK1:p352]
EndorphinThe 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
ProgesteroneProgesterone has sedative actions
* Increase 10-20 fold in 3rd trimester
ImplicationMAC of volatile agents is reduced by 30-40% during pregnancy
* Partly because of endorphins and progesterone
Epidural and CSF pressureEpidural 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 foetal1. Changes to CVS at birth2. Maternal3. Placental gas exchange
foetal circulation Before birth Umbilical vessels Umbilical vein x 1 Umbilical arteries x 2
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 clampedLoss of umbilical circulation --> Increase in systemic vascular resistance (SVR)
Step 2 - First breathFirst 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 gradientIncreased 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
Summary1. Loss of umbilical circulation 2. Large increase in pulmonary circulation 3. Closure of forman ovale 4. Closure of ductus arteriosus 5. Closure of ductus venosus
3.8.3. Placental gas exchangePlacental 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)
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