physiology of fetal circulation - university of illinois...
Post on 21-Aug-2020
6 Views
Preview:
TRANSCRIPT
1
Physiology of Fetal Circulation
G. Ganesh Konduri, MD
Medical College of WIMilwaukee, WI
Disclosure
• Plagiarism = Copy material from one source
• Research = Copy material from multiple sources
2
Outline
• Arrangement of fetal circulation• Different segments of fetal circulation
-Placenta – pulmonary circulation• Developmental changes• Transition at birth
Function of Circulatory System
• Provide oxygen and nutrient supply to the tissues
• Adjust the oxygen supply to the metabolic needs of the tissues
• Return deoxygenated blood and CO2 to the organ of gas exchange
3
Normal Fetus
Satyan
Fetal Circulation
4
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
PFO
Placental Circulation
5
DV
PDA
PFO
Arrows indicate sites of arterio-venous shunts in the placenta
Vessel PO2
Maternal Uterine art 90-100Inter-villous space 50Umbilical artery 20Umbilical vein 30-35
Chorionic villus
Branch Villus
Intervillous space(Maternal blood)
(50)
(20)(35)
() PO2
(100)
Hb-O2 Dissociation Curve
Fetal Hb=70% Term Neo
P50= 20-HbF, 28-HbA
90%= 45-HbF. 60-HbA
6
right shift left shift
temperature high low
DPG high low
p(CO2) high low
p(CO) low high
pH (Bohr effect) low (acidosis) high (alkalosis)
type of hemoglobin
adult hemoglobin
fetal hemoglobin
Hb-O2 Dissociation Curve
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
PFO
8535
70
5065
65
55
7
Oxygen Content of Blood at Different Levels of Oxygen Tension
PO2 (torr) SO2 (%) O2 Combined with Hb(ml/100ml)
O2 dissolved in plasma (ml/100ml)
Total O2content per 100ml of blood
25 (Hb=16) 65 13.95 0.075 14.01
90 (Hb=16)
90 (Hb=12)
100
100
21.4
16.08
0.3
0.3
21.74
16.38600 (Hb=16) 100 20.1 1.8 21.9
Modified from Cyanosis in the newborn infants – Joseph Kitterman, MD Pediatrics in Review Vol 4 (1) July 1982
Hb binds 1.34 ml O2/gmDissolved O2 = 0.3 ml/100 mmHg
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
PFO
8
Left LobeRight Lobe
3-9 mmHg10-20 cm/s
60-80 cm/s
30-50% of UV Blood across DV
9
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
PFO
Percent Combined Output20 Wks 30 Wks 38 Wks
Combined output
210 ml/min 960 ml/min 1900 ml/min
Left Ventr 47 43 40
Right Ventr 53 57 60
PFO 40 30 28
Lungs 5 10 12
10
Developmental Limitations
• 30% of fetal (premature) myocardial cell consists of myofibrils (60% of adult myocyte)
• Myofibrils less Ca++ sensitive• Mitochondrial size & complexity less in
fetus• More dependent on carbohydrate for
energy
Fetal/neonatal myocardial physiology
Fetus/ Neonate Adult
Cardiac output HR dependent SV & HR
Starling response limited normal
Compliance less normal
Afterload compensation limited effective
Ventricular high relatively low
interdependence
11
Changes at birth
• SVR increases suddenly • Pulmonary flow increases by 10-fold• Left ventricle-increases in pre-load
& after-load• Increased oxygen supply- improved left
ventricular performance
12
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
PFO
Response to Physiologic Stimuli
Stimulus PDA Pulm Artery
Hypoxia Dilate Constrict
Acidosis Dilate Constrict
Alkalosis Constrict Dilate
Oxygen Constrict Dilate
13
PGE2 Effects on PDA
Endothelial Cell
Smooth Muscle Cell
PGE2
cAMPPDE3
AMP
Relaxation
Low PO2 High luminal pressure
COX
Placental PGE2
EP2 EP3 EP4
K+ K+ATP
14
Normal Fetal
CirculationPlacenta UA
UVIVC
Liver
SVCAorta
Lung
PA
PV
DA
Portal Vein
Iliac Arteries
FO
15
20 weeks 28 weeks 36 weeks
• 40-Fold increase in # small blood vessels in 3 trimester
• Increase in smooth muscle layer around small PA
• Increase in responsiveness of PA to stimuli
Fetal Pulmonary CirculationSystemic Blood PressurePulmonary arterial pressure
16
Low PO2
↓NO, PGI2↑ET-1, EET, TxA2
↓cGMP, cAMP↑Ca++
↓K+Ca, Kv
Pre-pro-ET-1 Big-ET1
ET-1
ECE
ET-A
↑Ca++Contr
ET-B
↑eNOS
NO↓Ca++Relax
Endothelin Effects on Vessel
(203 AA)(92 AA)
(21 AA)
17
Vas
cula
r Res
ista
nce
Blo
od F
low
Arte
rial P
ress
ure
(mm
Hg/
ml/m
in/k
g)
(
ml/m
in/k
g)
(
mm
Hg)
50
40
30
20
10
0450
400
350
300
250
200
150
100
501.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0 95 136 Birth 1-3 6 days Age
80% decrease in 24 h
18
Transition of Lung at Birth
20 >100
4020
Fetus Newborn
Transition in Pulm Flow
0100200
300400500
600700
800
BL Drain lq Dist Dist+O2
Left
pulm
flow
(ml/m
in)
*
*
*
19
Oxygen
Hyperbar O2
3 Atm
Oxygen & Pulmonary Flow
0100
200300400
500600700
800
BL Norm O2 Hyperbar O2
Fetal PO2 22 27 47
Left
pulm
flow
(ml/m
in)
20
Oxygen & Pulmonary Flow
0100
200300400
500600700
800
BL Norm O2 Hyperbar O2
ControlN-LA
Fetal PO2 22 27 47
21
ATP AMPAden
NO PG
Oxygen
ADPPulmonaryartery Fetal RBC
Alveolus
0123456789
Bl 10% 21% 100%
ATP
0
200400
600
800
10001200
1400
0
0.25 0.5 1 2 4 8
ATP ADP AMP
Plasma ATP level (µM) Left Pulmonary Flow (ml/min)
*
*
*
** * *
**
**
***
ATP conc. µMFiO2
22
ATP, VEGF
Ligand
Receptor
Oxygen, Distension
eNOSL-arginine L-citrulline
NO
COX PGISAA
PGI2
AdenylateCyclase
PDE3PDE5
sGCGTP
cGMPGMP
ATP
AMP
cAMP
Pulmonary Artery
Pulmonary flow and Maturation of Pulmonary flow and Maturation of NOS & COXNOS & COX
0.4 0.8 birth0
20
40
60
80
100
120
Pul
m fl
ow a
s %
car
diac
out
put
0.4 0.8 Birth0
20
40
60
80
100
120
NOSCOX-1
23
BH4BH4
Serine 1177 Serine 1177 --PP
ThrThr--497 497 PP
NADPHNADPH HemeFe3+
OO22
OO22--..
CaveolinCaveolin--11
ee--ee-- ee--
LL--ArgArg
NHNH22IIIICCII
NONO O =CO =CII
LL--CitrCitr
Hsp90Hsp90
ee--ee--FMNFAD CaM
Akt
Reactive Oxygen Species
O2_• NO
eNOS
H2O2
H2O + O2
Peroxynitrite
Constriction
SOD
cGMP
Vasodilation
NOX, NOS
24
↑eNOS ↑COX ↑SOD
↑ NO ↑ PGI2
↑cGMP ↑cAMP
Endo
Smoothmuscle
Estrogen, Steroids, Shear stress
↓O2_•
Regulation of cGMP
NOS
↑↑cGMPcGMP
sGCsGCpGCpGC
NOANPBNP CO
Relaxation
CNP
Endo
Smoothmuscle
25
AIR
O2 O2
AirCONOANPBNPPGI2K+v
Postnatal Circulation
26
Summary
• Fetal circulation uniquely adapted to the intra-uterine life- Low PO2 and non-respiring lungs
• Preparation for post-natal adaptation occurs throughout fetal life
• Understanding these adaptations essential to management of infants in NICU
27
Normal Post natalCirculation
Normal TransitionSystemic Blood Pressure
Pulmonary arterial pressure
Left Atrium
Right Atrium
28
O2 Saturations in Fetal Circulation
Ductus Venosus Shunt
• 30-50% of umbilical venous blood shunted thru DV
• Percent shunted declines with gestation• Rest of umbilical venous blood-left and
right lobes of liver• Left hepatic vein (65% Sat)-across PFO• Portal venous blood (40% Sat) mostly to
right lobe of liver
29
PDA - Compensatory Mechanism?
EC SMLumen
Low PO2Lumen pressure
eNOS
Cox1,2
Hox 1,2
Oxygen↓Pressure
ET-1
Cyp 450
NO ↑cGMP
PGE2 ↑cAMP
CO ↑cGMP
↑Ca++
↓Kv
↑Kv
PDA Physiology
30
Flow Across PDA
• Regulated by PVR in the fetus• Response to blood gas changes- opposite
to pulmonary circulation• Response to vasoactive substances-
PGE2, NO, ATP, K+ channel blockers etc similar to pulmonary vessels
31
Breath NO Levels Breath NO Levels -- InfantsInfants
0
20
40
60
80
100
120
140
Preterm Term
Nasal NO Ex NO-VentPa
rts p
er b
illio
n
Williams et al Ear Hum Dev ’03Leipala et al Eur J Ped ‘04
Right Lobe Left Lobe
DV
Portal
Vein
32
EC VSMLumen
Low PO2↑Lumen pressure
↓eNOS
↓Cox1,2
↓Hox 1,2
↑ET-1↑Cyp 450
↓cGMP
↓cAMP
↓cGMP
↑Ca++
↓Kv
↑Ca++
ETA
EET
↑Lip OxyTxA2TxB2
Fetal Pulmonary Artery
EC VSMLumen
EstrogenSteroidsShear Stress
↑eNOS
↑Cox1,2
SOD-1,2
↑GC
↑AC
↓SMC growth
↑Kv
↓Ca++
Maturation of vasodilator system during gestation
33
Basal ATP levels in fetus
0 800
PA PA Sat 59%
LA LA Sat 81%
0 5
PA
LA
Blood ATP
Plasma ATP
*
*
Advantages of sheep model
Gest age 140 daysCarry single or twinsFetus large enough for instrumentationUterus is quiescent
34
Superoxide Dismutases
NOSOO22
GCGC--cGMPcGMPKK++
NONONOSNOS
EndoEndo SMCSMC
COXCOX PGI2PGI2 ACAC--cAMPcAMPDistDist
top related