Maternal Physiology PDF

MATERNAL PHYSIOLOGY (a) To explain the cardiovascular and respiratory changes during pregnancy, their causes, and their consequences. (b) To explain the consequences of the supine posture during pregnancy. (c) To outline the functions of the placenta. (d) To describe the transfer of gases bet...

MATERNAL PHYSIOLOGY (a) To explain the cardiovascular and respiratory changes during pregnancy, their causes, and their consequences. (b) To explain the consequences of the supine posture during pregnancy. (c) To outline the functions of the placenta. (d) To describe the transfer of gases between mother and foetus including the double Bohr and Haldane effects. (e) To describe the endocrine changes that occur during pregnancy and their consequences. (f) To describe the haematological changes with pregnancy. (I) Maternal Physiological Changes During Pregnancy: Important to note → Physiological changes occur in pregnancy due to 4 key factors: - (1) Hormonal changes (Eg. progesterone, oestrogen, HPL, hCG) - (2) Mechanical effects of enlarging uterus - (3) ↑ metabolic demands (Eg. MRO2 ↑ by 20% at term) - (4) Placental circulation acting as low pressure AV shunt CVS changes during pregnancy: - (1) ↑ HR (by 15% at end of 1st TM → then by 25% by mid 3rd TM) - (2) ↑ SV (by 20-30% from 8/40 to 32/40) → due to ↑ BV (40%) - (3) ↑ C.O. (by 30% from 8/40 to 32/40) → due to ↑ HR, ↑ SV (a/w ↑ BV), ↓ TPR (a/w ↑ VR), and ↑ MRO2 - (4) ↓ SVR (by 20-30% by end of 1st TM) → due to (i) placental circulation (10% of C.O.) acting as a low resistance AV shunt, and (ii) progesterone and PG-mediated peripheral vasodilation (esp renal, splanchnic, heart, breasts, skin circulation) - (5) ↓ PVR (by 35% by end of 1st TM) → due to progesterone/prostaglandins - (6) ↑ tissue blood flow (esp to uterus/placenta, heart, kidneys, GIT, breasts, skin) → due to (i) ↑ C.O. and (ii) hormone-mediated regional vasodilation – Nb. CBF is NOT affected!!! - (7) ↓ BP (↓ MAP, ↓ DBP > ↓ SBP) by 10% (esp at 20/40) due to ↓ SVR → BUT this normalizes towards term - (8) CVP and PCWP unchanged - (9) Aortocaval compression o Abdominal aorta and IVC may be occluded by effects of gravid uterus as early as 2nd TM (max. effect at 36-38/40), especially when supine → characterised by:  (i) Complete compression of IVC:  85% of ♀– Compensatory vasoconstriction, tachycardia and collateral blood flow (venous return diverted via paravertebral and epidural veins into azygous system → SVC) maintains VR/C.O. and MAP  15% of ♀ – “Supine hypotension syndrome” occurs as compensatory mechanisms are insufficient → results in ↓ VR/C.O. and MAP → causes hypotension, bradycardia, pallor, syncope, N/V, sweating  (ii) Partial compression of abdominal aorta → causes ↓ uteroplacental BF by 20% (causing foetal distress) and ↓ renal BF o This is prevented by positioning mother on left side  Note – During labour: - (i) C.O. – ↑ 15% (early labour),↑ 30% (1st stage), ↑ 45% (2nd stage), ↑ 65% (post- partum), then normalizes 2/52 post-partum - (ii) Uterine contractions and uterine involution post-partum squeezes 300 mL of blood out of uterus into circulation (“Autotransfusion”) causes ↑ VR → ↑ SV/C.O. - (iii) BP – ↑ 10-20 mmHg with uterine contractions. Normalises 2/52 post-partum - (iv) CVP ↑ (4-6 cmH2O) due to ↑ VR a/w autotransfusion Respiratory changes during pregnancy: - (1) Anatomical changes to thorax and airway: o (i) Diaphragm displaced up 4 cm by gravid uterus → but contractility not markedly restricted o (ii) ↑ AP and transverse diameter by 2-3 cm (so ↑ circumference by 5-7 cm) → due to “Relaxin” (from corpus luteum) that relaxes ligaments of ribs o (iii) Upper respiratory tract (Ie. vocal cords, nasal mucosa) swollen → due to capillary engorgement - (2) Changes in lung volumes: o Occur early in pregnancy and continue to change progressively during pregnancy (esp from 20/40) → normalize 2-5 days post-partum o ↓ ERV and RV (incl FRC and TLC) → due to (i) elevated diaphragm (2° gravid uterus) and (ii) ↑ pulmonary blood volume IRV (u/c; 2050 mL) IC (↑ 5%; 2500 to VC (u/c; 3200 mL) TLC (↓ 5%; 4200 to TV (↑ 30%; 450 to 2650 mL) 4100 mL) 600 mL) ERV (↓ 20%; 750 to FRC (↓ 20%; 1700 to 550 mL) 1350 mL) RV (↓ 20%; 1000 to 800 mL) Note – FRC ↓ by 70% of sitting value when supine (due to effects of gravid uterus on diaphragm) - (3) ↑ minute and alveolar ventilation: o ↑ early (esp after 10/40) and continues to ↑ gradually during pregnancy (↑ by 50-70% at term) → due to (i) ↑ TV (by 40% at term) and (ii) ↑ RR (by 15% at term) o Caused by progesterone-mediated stimulation of medullary respiratory centres → ↑ sensitivity to PaCO2 (left shift in CO2 response curve) o During labour – ↑ MV/AV further (by 160%) due to pain and ↑ MRO2 a/w uterine contractions → can cause transient ↓ PaCO2 (to 20 mmHg!) - (4) ABG changes: Normal ABG Pregnancy ABG Important points pH 7.40 7.42 - ↑ MV (esp at end of 1st TM → causes (i) ↓ PCO2 and (ii) ↑ PO2 → this creates PCO2 40 30 favourable pressure gradients of O2/CO2 (mmHg) across placenta for exchange with foetus! PO2 95 105 - ↓ PCO2 causes a respiratory alkalosis BUT (mmHg) Δ pH is compensated renally (by ↑ HCO3- HCO3- 24 20 excretion/↓ BE) → this prevents a shift in (mmol/L) Hb ODC (despite ↓ PCO2) BUT ↓ BE 0 -2 maternal buffering capacity (mmol/L) - ABG changes normalize rapidly post- partum - (5) Changes in lung mechanics: o (a) Work of breathing unchanged → due to balance b/t (i) Non-elastic forces (↓ AWR) and (ii) Elastic forces (↓ total compliance of respiratory system) o (b) ↓ AW resistance (by 35%) and ↑ anatomical DS (by 45%) → due to progesterone- mediated large AW dilation o (c) ↓ total compliance of respiratory system → due to ↓ CW compliance 2° to elevation of diaphragm by gravid uterus (Nb. lung compliance is unchanged) o (d) F-V curves unchanged (while sitting) o (e) AW closure (and atelectasis) when supine only → up to 50% ♀ have FRC < CC when supine (otherwise FRC remains > CC when sitting) - (6) ↑ tissue O2 delivery to tissues: o ↑ O2 flux (by 10% at term) → due to (i) ↑ C.O. (main), (ii) ↑ PO2, and (iii) ↑ tissue BF (a/w regional vasodilation) → despite limitations in CaCO2 by (i) Anaemia of  pregnancy, (ii) Right shift in Hb ODC (due to ↑ 2,3-DPG), and (iii) Hb being maximally saturated o ↑ tissue MRO2 during pregnancy (by 20% at term) Haematological changes during pregnancy: - (1) Physiological anaemia of pregnancy: o From 6-8/40 to 28-32/40 → ↑ BV by 40% (1.2-1.5 L) due to (i) ↑ PV by 50% (due to Na+/H2O retention by oestrogen activation of RAAS) and (ii) ↑ RCV by 30% (due to renal EPO synthesis) o BUT ↑ PV > ↑ RCV and ↑ PV occurs faster than ↑ RCV → thus, ↓ RBC count (4.6 to 3.6 x 106/mm3), ↓ Hb (140 to 120 g/L) and ↓ Hcrit (41 to 35%) by 28-32/40 - (2) ↓ platelets (5-20%) due to haemodilution (can result in gestational thrombocytopaenia - (3) ↑ WCC (9000/mm3) due to ↑ PMNL and monocytes - (4) Acquired hypercoagulable state → prepares for blood loss at delivery o ↑ coagulation – ↑ CF VII, VIII, IX, X, XII and fibrinogen, but ↓ ATIII → ↓ APTT/PT (20%) and bleeding time (10%) o ↑ fibrinolysis – ↑ plasminogen and fibrin/FDP formation, but ↓ tPA and CF XIII (fibrin-stabilising factor) - (5) ↑ total amount of proteins BUT [ ]’s are variable: o ↓ [ ] – Total proteins, γ-globulins and albumin → due to haemodilution o ↑ [ ] – Total globulins (esp α and β-globulins), fibrinogen and CRP - (6) ↓ plasma oncotic pressure (14%) due to ↓ [albumin] → ↑ oedema - (7) ↑ ESR due to ↑ plasma globulin/fibrinogen - (8) ↓ pseudocholinesterase activity (20-30%) at end of 1st TM Endocrine changes during pregnancy: - (1) Placenta produces 4 hormones: o (i) Human chorionic gonadotrophin (hCG)  Peptide hormone synthesized by syncytiotrophoblast cells) → ↑ until it peaks at 10-12 weeks, then ↓ till term  Role – Maintains corpus luteal function during 1st TM (oestrogen and progesterone production) that maintains pregnancy until placenta takes o (ii) Human placental lactogen (hPL)   Peptide hormone → ↑ throughout pregnancy and it peaks near term  Role – Promotes foetal growth by regulating maternal metabolism → secretion is ↑ by ↓ maternal BGL → exerts “insulin antagonist” effect (favours lipolysis and FFA usage in mother to spare glucose for use in foetus) o (iii) Oestrogen and progesterone  Steroid hormones produced by corpus luteum in 1st TM and then the placenta using precursors derived from foetal adrenal cortex → levels ↑ gradually until term  Role – Responsible for several maternal physiological changes - (2) Pituitary gland: o ↑ PRL, ↑ ACTH, ↑ MSH o ↓ GH (by HPL) and ↓ FSH/LH (by oestrogen/progesterone) - (3) Others: o ↑ cortisol (due to ACTH) o ↑ renin/AII and ↑ aldosterone (due to ACTH/progesterone) o ↑ T3/T4 o ↑ PTH (due to Ca2+ transfer to foetus) o ↑ prostaglandins (PGA ↑ in 1st TM; PGE ↑ in 3rd TM) Metabolic changes during pregnancy: - (1) ↑ BMR and MRO2 by 20% at 36/40, then ↓ to 15% above baseline at term → due to ↑ demands of foetus, hypertrophy of maternal tissues (breast/uterine), ↑ cardiorespiratory work a/w pregnancy - (2) Metabolism of metabolic fuels o (a) CHO  ↑ BGL due to ↑ HPL (causes ↓ insulin sensitivity/glucose intolerance due to “insulin antagonist” effects), ↑ cortisol, ↑ oestrogen/progesterone → causes ↑ placental glucose transfer for foetal use, gestational DM and glycosuria  ↑ insulin levels from end of 1st TM to 32/40, then ↓ to baseline at term → due to ↑ BGL o (b) Fat  Fat is stored in 1st half of pregnancy (for use later in pregnancy)→ ↓ plasma [ ] of FFA/glycerol, cholesterol and phospholipids  Fat is mobilized in 2nd half of pregnancy (due to ↑foetal growth in 3rd TM) → ↑ plasma [ ] of FFA/glycerol, cholesterol and phospholipids → ↑ placental transfer for foetal use (esp fat synthesis in foetal liver) o (c) A.a. → ↓ maternal plasma [a.a] due to ↑ hepatic gluconeogenesis (to ↑ BGL), placental transfer for foetal use (energy/protein synthesis) and urinary losses  - (3) ↑ maternal weight → due to ↑ uterine/breast tissue mass (progesterone/oestrogen), ↑ ECFV (by 3 L at term), and ↑ fat stores (3 kg) GI changes during pregnancy: - (1) ↑ gastro-oesophageal reflux (all 3 trimesters) due to: o (a) Incompetent LOS function → (i) ↓ LOS tone (progesterone, narcotics, anticholinergics, diazepam) and/or (ii) changes in angle of gastro-oesophageal junction by pressure effects of gravid uterus o (b) ↑ IGP (gravid uterus effect) - (2) ↓ GI motility o (a) ↓ gastric motility and emptying at 12-14/40 (end of 1st TM) due to progesterone- mediated GI SM relaxation (4-8 hrs) → during labour, gastric emptying esp prolonged (4-8 hrs) due to anxiety, pain, narcotic effects o (b) ↓ intestinal motility due to effects of progesterone and ↓ motilin o (c) ↓ GB contraction (2nd and 3rd TM) due to progesterone-mediated ↓ in CCK - (3) ↑ gastric acid volume (> 25 mL) and acidity (pH < 2.5), esp during 3rd TM and labour → due to ↑ gastrin (by placenta) - (4) Cephalad displacement of stomach/intestines by gravid uterus → ↑ IGP - (5) Hepatic changes: o HBF unaltered during pregnancy o Fatty changes, glycogen depletion, lymphocytic infiltration, SER proliferation (↑ CYP450 activity) and ↑ ALP levels Renal changes during pregnancy: - (1) ↑ GFR (50%) and RBF (75%) during 1st TM due to ↑ C.O. → a/w ↓ plasma [ ] of urea and creatinine in 1st and 2nd TMs - (2) Glycosuria → due to ↑ GFR, ↑ BGL and ↓ renal threshold (↓ tubular reabsorption) - (3) Proteinuria (due to ↑ renal venous pressure ↓ renal threshold (↓ tubular reabsorption)) and ↑ excretion of a.a. (due to ↑ plasma [a.a.]) - (4) ↑ HCO3- excretion (plasma [ ] 18-21 mmol/L; BE -2) → compensation for respiratory alkalosis - (5) ↑ RAAS effects on kidneys - (6) Dilation of renal pelvis, calyces and ureters (from 2nd/3rd month of pregnancy) → due to obstruction of urine flow by gravid uterus CNS changes during pregnancy: - (1) Analgesia from β-endorphins and enkephalins (from placenta) → levels ↑ significantly with uterine contractions during labour/delivery - (2) ↑ sedation due to progesterone - (3) ↑ EDV engorgement due to ↑ IAP → ↑ pressures to + 1 cmH2O during pregnancy, + 4- 10 cmH2O during labour, up to + 60 cmH2O when bearing down - (4) CSF unaltered during pregnancy (but ↑ 70 cmH2O when bearing down) Musculoskeletal changes during pregnancy: - Relaxin from placenta → causes ligament relaxation and lumbar lordosis (II) Anaesthetic Implications of Maternal Physiological Changes: (1) ↑ risk of hypoxaemia and desaturation: - (a) ↓ maternal O2 reserve due to – (i) ↓ FRC (by 20% at term), and (ii) ↑ MRO2 (by 20% at term) a/w ↑ metabolic rate → causes rapid desaturation/hypoxaemia (even with brief period of apnoea) → thus, very good preoxygenation is required prior to a GA! - (b) Difficult intubation due to anatomical changes (Ie. UAW swelling, large breasts) → risk of prolonged period of apnoea → risk of desaturation/hypoxaemia (2) Changes in anaesthetic requirements: - GA: o (a) Rapid induction/recovery from volatile anaesthesia due to ↑ wash-in/wash-out → (i) ↑ alveolar ventilation (by 50-70% at term) and (ii) ↓ FRC (by 20% at term), although this is partly offset by ↑ C.O. (by 30-40% at term) o (b) ↓ dose of anaesthetic agents → (i) MAC ↓ 40% (due to progesterone/β- endorphins, (ii) ↓ induction dose of STP by 35% (due to ↑ Vd and elimination), (iii) ↑ sensitivity to vecuronium (as ED50 ↓ by 50%) - Neuraxial block: o (a) ↓ LA dose required (by 25-30% at any stage of pregnancy) due to → (i) ↑ spread of LA (esp at 2nd TM due to distension of EDV), (ii) ↑ sensitivity of nerve fibres to LA, and (iii) ↑ diffusion of LA to membrane receptor sites o (b) ↑ risk of bloody tap due to distension of EDV (esp during contractions) (3) Risk of aorto-caval compression: - Abdominal aorta and IVC may be occluded by effects of gravid uterus as early as 2nd TM (max. effect at 36-38/40), especially when supine → characterised by: o (i) Complete compression of IVC:  85% of ♀– Compensatory vasoconstriction, tachycardia and collateral blood flow (venous return diverted via paravertebral and epidural veins into azygous system → SVC) maintains VR/C.O. and MAP  15% of ♀ – “Supine hypotension syndrome” occurs as compensatory mechanisms are insufficient → results in ↓ VR/C.O. and MAP → causes hypotension, bradycardia, pallor, syncope, N/V, sweating o (ii) Partial compression of abdominal aorta → causes ↓ uteroplacental BF by 20% (causing foetal distress) and ↓ renal BF - This is prevented by positioning mother on left side (4) ↑ aspiration risk during GA: - (a) ↑ gastro-oesophageal reflux (all 3 trimesters) due to → (i)↓ LOS tone (progesterone, narcotics, anticholinergics, diazepam), (ii) ↑ IGP (effect of gravid uterus) and (iii) altered gastro-oesophageal junction angle (due to effects of gravid uterus) - (b) ↓ GI motility/emptying (at 12-14/40; end of 1st TM) due to progesterone → prolonged further during labour (by 4-8 hrs) due to anxiety, pain, narcotics - (c) ↑ gastric acid volume (> 25 mL) and acidity (pH < 2.5), esp during 3rd TM and labour → due to ↑ gastrin (by placenta) - (d) Difficult intubation due to anatomical changes (III) Physiology of the Placenta: Functions of the placenta: - (1) Endocrine organ of pregnancy → produces hCG, HPL, oestrogen, progesterone (see above for details) - (2) Immunological function o (a) Immunological barrier function  Protects foetus from rejection by maternal immune system  Mechanism – (i) Inability of trophoblasts to present Ag to maternal lymphocytes (as they do not express MHC), (ii) Acquired defects in maternal immunocompetence o (b) Protects foetus from infection  Permits transport of maternal IgG to foetus (Nb. IgG is the ONLY Ab class that can cross placenta) → provides passive immunity to foetus for first few months post-birth  Mechanism – Syncytiotrophoblast contains receptors for Fc fragment of IgG → IgG is endocytosed into a vesicle → then released into foetal blood Note – Issues: - (i) Rh isoimmunisation – Maternal Ab against foetal RBC can cross placenta → cause foetal haemolysis - (ii) Foetal autoimmune diseases (Eg. myasthenia gravis, thrombocytopaenia, thyroid diseases) can occur as maternal autoimmune IgG Ab’s can cross placenta - (3) Transport substances b/t maternal and foetal plasma o Gas exchange (O2/CO2), nutrient transfer (glucose, a.a., lipids, vitamins), wastes removal (urea/bilirubin), H2O/electrolyte exchange and drug transfer across placental barrier via various transport mechanisms (see below for details) - (4) Metabolic functions → synthesizes glycogen, FA, cholesterol and various enzymes (Eg. sulfatase, pseudocholinesterase, ALP, MAO and COMT) Anatomy of the placenta: - “Chorionic villus” is the basic structural unit of the placenta → it is a vascular projection of foetal tissue that is bathed by maternal blood within the “Intervillous space”. It consists of: o (i) Foetal connective tissue containing foetal capillaries o (ii) Chorion → outermost layer of foetal tissue that is made of 2 layers → (a) Syncytiotrophoblast (directly contacts maternal blood in intervillous space) and (b) Cytotrophoblast (b/t syncytiotrophoblasts and foetal CT)  Important to note – Substances traverse between foetal and maternal blood via the following layers: Maternal blood (intervillous space) ↔ Chorion (2x layers of trophoblasts) ↔ Foetal connective tissue ↔ Endothelium of foetal capillaries ↔ Foetal blood - Uteroplacental blood supply: o Uterine and Ovarian arteries → form Arcuate arteries → form Radial arteries that arise and penetrate myometrium o Radial arteries then divide into → (i) Spiral arteries (ejects blood into intervillous space), and (ii) Basal arteries (supply myometrium and deciduas) o Maternal blood within “Intervillous space” bathes the chorionic villi → then drains into venous openings that lead into the Uterine veins - Foetal blood flow in chroionic villi → derived from paired Umbilical arteries → flows into capillaries within chorionic villi → then into Umbilical vein Aside – Efficiency of foetal-intervillous blood flows: - Should act as an efficient “counter-current system” (Ie. flow on both sides run in opposite directions) → BUT due to shunting it is no more efficient than a “concurrent system” (Ie. flow on both sides run in same direction) - This inefficiency in placental barrier transfer is attenuated by maternal blood flow being 2x > than umbilical blood flow Factors determining placental transfer of substances: - (1) Mechanism of placental membrane exchange: o (a) Simple passive diffusion  Small and/or lipid soluble substances (such as respiratory gases (O2/CO2), electrolytes (Na+/Cl-), lipids (FA, steroids, fat-soluble vitamins) and most drugs) diffuse across the placental barrier down their [ ] gradients without use of energy  Rate of transfer follows “Fick’s Law of Diffusion”: J = D x A x dC dT  Where: - [ ] gradient across placental barrier (dC) – determined by: o (i) Maternal-foetal arterial [ ]GRADIENT o (ii) Maternal intervillous space and foetal placental blood flows o (iii) Diffusing capacity of placenta for the substance o (iv) Protein binding/dissociation rates of substance o (v) Metabolism of substance by placenta (Eg. O2) - Surface area of placental barrier (A) – Exchange area = 1.8 m2 (Nb. total villous area = 16 m2) - Thickness of placental barrier (dT) – 3.5 um - Diffusion capacity of substance by placenta (D) – determined by substance’s: o (i) MWT – Impermeable if > 6 kDa; diffusion related to other factors if < 1 kDa o (ii) Lipid solubility – Diffusion rate α to lipid solubility o (iii) Degree of ionization – Electrical charge deters placental transfer → Nb. “Ion trapping” of basic drugs can occur on foetal side due to ↑ acidity there (cf. maternal side of placenta) o (iv) Protein binding/dissociation rate – diffusion α to % free form o (b) Facilitated transport – Substances (such as glucose, lactate, a.a., electrolytes (Na+, H+)) are transported across the placental barrier via a membrane protein carrier down their [ ] gradients without use of energy → rate of transfer is determined by Fick’s Law of Diffusion (see above), BUT occurs much faster than simple passive diffusion o (c) Active transport – Substances (such as H2O-soluble vitamins, a.a., I2, Fe2+, and electrolytes (K+, Ca2+, PO43-)) are transported across the placental barrier via a membrane protein carrier against their [ ] gradients with the use of energy (as ATP) o (d) Endocytosis – Large/non-lipid soluble substances that are not transported by a carrier protein (such as IgG, globulins, lipoproteins) are taken up in small vesicles and then exocytosed on the other side of the placental barrier o (e) Bulk flow – H2O (and solutes via “solvent drag”) moves across the placental barrier according to Starling forces (PHYDROSTATIC and POSMOTIC) across the barrier o (f) Breaks – Delicate parts of chroionic villi break off within IVS and release contents into maternal circulation (Eg. foetal RBC) - (2) Uteroplacental blood flow o At term → uteroplacental BF is 500-700 mL/min (10% maternal C.O.) of which:  (i) 70-90% of this BF enters the intervillous space (via the spiral arteries) → NOT autoregulated as blood flow is “pressure-dependent” (see factors below)  (ii) 10-30% of this BF supplies the myometrium/deciduas (via the basal arteries) → autoregulated blood flow o Blood flow to the intervillous space (which participates in substance exchange with foetal blood) is affected by the following factors: UBF = (UAP – UVP) UVR (1) Uterine arterial pressure (UAP): - Maternal arterial BP → ↓ MABP (Ie. due to SNS block 2° neuraxial block, hypovolaemia, supine hypotension syndrome, Etc.) causes ↓ UAP → ↓ UBF (2) Uterine venous pressure (UVP): - Uterine tone and contractions → ↑ tone/contractions (Ie. due to contractions, oxytoxics, ketamine, Etc.) causes ↑ UVP → ↓UBF (3) Uterine vascular resistance (UVR): - Uterine arteriolar tone → ↑ vasoconstriction (Ie. a/w essential HT and PET, α- adrenoceptor stimulation (by endogenous SNS innervation, catecholamines or sympathomimetics), and vasopressin) causes ↑ UVR → ↓ UBF  - (3) Umbilical blood flow o At term → umbilical BF is 360 mL/min (25-50% of foetal C.O. (≈ 1000 mL/min)) o It is “autoregulated” (cf. uterine BF) → involves vasodilators (PCI-2/NO) derived from vascular endothelium o BF is ↓ with severe hypoxia, ↑ BGL, catecholamine and cord compression - (4) Placental surface area available for exchange - (5) Placental metabolism o Consumption of substance by placenta (Eg. O2) → ↓ amount available for transfer Placental gas exchange: - O2/CO2 exchange across the placenta occurs by “flow-limited passive diffusion” (as they are small hydrophobic molecules that are very permeable within the placental barrier) → the rate of diffusion is thus determined by “Fick’s law of diffusion” (See above) Important to note – Gas exchange across the placenta is very inefficient cf. that in an adult lung (Ie. placenta only exchanges 1/10th the amount of O2 as the adult lung) → due to: - (1) ↑ diffusion distance in the placenta → 3.5 um (vs 0.5 um in the lung) - (2) ↓ gas permeability in the placenta → permeability of blood-blood barrier of placenta is much less than the blood-gas barrier of lung - (3) ↓ total surface area of the placenta → 16 m2 at term (vs 50-60 m2 in the lung) - O2 exchange across the placenta → determined by the following factors: o (1) Rates of maternal and foetal blood flows → MAIN factors  (i) Maternal (intervillous space) blood flow → determined by factors that influence Uterine BF (see above)   (ii) Foetal (placental) blood flow → determined by factors that influence Umbilical BF (see above) o (2) Maternal-foetal PO2 gradient  PO2 gradient of ≈ 30 mmHg exists between maternal blood in intervillous space (~ 50 mmHg) and foetal blood in umbilical artery (~ 20 mmHg) → O2 diffuses down its [ ] gradient from maternal to foetal blood o (3) Maternal-foetal Hb O2 affinity  (i) Double Bohr effect → 2-8% of transplacental O2 transfer Note – “Bohr Effect” → ↑ PCO2/↓ pH causes a right shift in Hb O2 dissociation curve → conformational change in Hb resulting in ↓ affinity for O2  When foetal blood releases CO2 → ↑ pH (7.21 to 7.32) and ↓ pCO2 (from 55 to 40 mmHg) of foetal blood → left shift in O2 Hb DC → ↑ affinity for O2 → ↑ O2 uptake across placenta from maternal blood  CO2 released from foetus is taken up by maternal blood → ↓ pH (7.42 to 7.3) and ↑ pCO2 (from 32 to 45 mmHg) of maternal blood → right shift in O2 Hb DC → ↑ O2 unloading → ↑ O2 crosses placenta to foetal blood  (ii) Hb type  HbF (in foetal blood) has a ↑ O2 affinity than HbA (in maternal blood) → P50 20 mmHg (HbF) vs P50 26.6 mmHg (HbA) → assists O2 unloading in maternal blood and O2 uptake across placenta into foetal blood Note – HbF has a relative left shift in O2 Hb DC and ↑ O2 affinity (cf. HbA) → b/c it lacks β-chains (Ie. HbF is α2γ2 cf. HbA which is α2β2) and thus cannot bind 2,3-DPG o (4) Maternal-foetal O2 carrying capacity in blood  Foetal blood has a ↑ O2 carrying capacity cf. maternal blood → due to 40% ↑ in [Hb] (190 g/L vs 120 g/L) o (5) Placental O2 consumption  Placenta consumes 20-30% of transferred O2 - CO2 exchange across the placenta → determined by the following factors: Note – CO2 exists as HCO3 (60%), carbamino- Hb (30%), dissolved CO2 (10%) → dissolved CO2 and HCO3 are the main forms of CO2 placental transfer o (1) Rates of maternal and foetal blood flows → MAIN factors  (i) Maternal (intervillous space) blood flow → determined by factors that influence Uterine BF (see above)  (ii) Foetal (placental) blood flow → determined by factors that influence Umbilical BF (see above) Note – CO2 is 20x more diffusible than O2 (as it is more soluble) → thus, CO2 exchange is influenced more by rates of maternal-foetal BF (cf. O2) o (2) Maternal-foetal PCO2 gradient  PCO2 gradient of ≈ 13 mmHg exists between foetal blood in umbilical artery (~ 50 mmHg) and maternal blood in intervillous space (~ 37 mmHg) → CO2 diffuses down its [ ] gradient from foetal to maternal blood o (3) Maternal-foetal Hb CO2 affinity  “Double Haldane effect” → accounts for 46% of transplacental CO2 transfer Note – “Haldane Effect” → Hb can ↑ capacity for CO2 carriage (as HCO3-) for a given PCO2 when it is in its deoxygenated state  ↑ O2 unloading from maternal blood → causes ↑ CO2 carriage capacity of maternal blood (as carbamino-Hb) for a given PCO2 → results in ↑ CO2 transfer from foetal blood across placenta  ↑ O2 loading of foetal blood → causes ↓ CO2 carriage capacity of foetal blood for a given PCO2 → facilitates further CO2 transfer to maternal blood o (4) Maternal-foetal CO2 carrying capacity in blood  Foetal blood has a ↑ CO2 carrying capacity cf. maternal blood (as carbamino- Hb) → due to 40% ↑ in [Hb] (190 g/L vs 120 g/L) o (5) LeChatelier effect  CO2 transfer from foetal to maternal blood favours a equilibrium shift in the “carbonic anhydrase” reaction → results in ↑ CO2 production from association H+ and HCO3- in foetal blood → results in more CO2 for transfer! H+ + HCO3_ ↔ H2CO3 ↔ CO2 + H2O