Yagel - Placental Circulation

Placental Fetal Circulation (Yegal05)

-Week 4-5 GA- chorionic villi form & surround the entire gestational sac until week 8-9 GA

-3-4th Month GA- villi become elaborately branched, forming the definitive placenta on one pole, while the ones on the other pole degenerate to form placental membranes

-uteroplacental circulation dilates much, w rapid villious angiogenesis--> placental dvp for fetal growth

-Uterus loses innervation; and no placental or cord innervation

-High flow, low resistance circ in placenta is needed; and due to the incr in diam of the vasc bed (as oppose to the length of the vasc network and the blood viscosity which have little impact).

Normal Uteroplacental Circulation Development

-Uterine vasc network anastomoses w ovarian and vaginal arteries to --> vasc arcade to perfuse the internal genitals

-Uterine Artery gives off 8-10 arcuate branches, extend inward to 1/3 thickness of myometrium to envelop the ant and post walls of the uterus.

-These arts --> radial arteries, then spiral arteries which enter the endometirum

-Physiological Transformation of Uterine Circulation

-uterine arteries transform to supply incr Q, induced to grow by the invasive trophoblast cells of fetus

-Spiral arteries remodel- lose myocytes fr media and internal elastic lamina--> more responsive to vasoactive chemicals; transformation done at mid pregnancy

-small caliber spiral vessels change into flaccid, distended arteries; unlike other vessel types, these INCREASE in diam as they approach the organ, not decrease...

-->optimize Q distrib in a low-resistance uterine vasc network and to the placenta...

-placenta limits (not facilitates) O2 supply to fetus during organogenesis...

-Development of Intervillous Circulation

-in the placenta, = an open system where blood is retained within arteries, through cap beds to veins

-the spiral arts open into ~a large lake of blood and the intervillous space does not --> resistance to Q, the placenta is like a big a-v shunt

-but initially, this isnt the case, the invasive trophoblasts that are near the uterine arteries act as a plug at the arteries' tips, to filter maternal blood, permit slow seepage of plasma without true bloo flow into the intervillous space. Supplemented by uterine gland secretions dicharged into intervillous space till 10 weeks GA

-O2 delivery is very well controlled, and fluctuates throughout the pregnancy

-balance bn metabolic needs of fetus/placenta and the danger of O2 free radicals

-initially, fetus dvps under low O2 condition- blood is sluggish, intervillus space is thicker, etc,

-the trophoblasts are Sn to free radicals, thus incr miscarriage w IDM bc it's assoc w incr free radicals

-Oxidative stressors are at times Nl in the pregnancy:

-at 8-9 weeks GA, uteroplacenta circ isn't plugged by the rophoblastic shell, allowing a limited maternal Q to enter the placenta at this time, this --> higher oxygen concentrations locally, at a time when trophoblasts aren't in high [ ] , so higher oxidative damage exposure --> focal troph. damage, --> villous degeneration, and trigger formation of fetal membranes--> needed for vaginal deliver later on.

-Q fr spiral arts to intervillous space is often intermittent, fr spont vasoconstriction' --> intermittent perfusion --> intermittent ischemia/reperfusion injury especially toward term when the fetus and placenta extract large quantities of O2 fr intervillous space, this may --> upregulate anti-free radical defense in placenta to reduce the oxidative stress. --> may cause remodeling of placenta needed...

-by end of first Tri, troph plugs are progressively dislocated, --> allow maternal Q freely and cont'ly to intervillous space. By 10-14 week GA transitional phase, 2/3 of primitive placenta disappears, the exocoelomic cavity is gone bc of amniotic sac growth, and maternal Q flows progressively throughout the entire placenta. --> maternal blood closer to fetus, better nutrition/exchange...

-Maternal Hemodynamic Changes & Uteroplacental Circulation Regulation

-mom's plasma volume increases to 40% more than Nl by its plateau in the 3rd Tri

-CO increases 30-60%; SVR drops 10%, much in the 1st Tri; CO increases more later on too

-PL and AL drop as SVR drops, HR increases to compensate, along w volume retention.

-Hct increases (as does viscosity)- fr 18-30% more than Nl value; but plasma volume increases 40%, so net--> hemodilution and the maternal Hct and viscosity drops...; lower maternal viscosity potentiates the drop in SVR

-... hormonal influences

-US/Doppler Features of Uteroplacental Circulation

-bc they are so dynamic, hard to make sense of just a single uteroplacental art interrogation

-In non-preg women & in 1st half of PG, the unterine arts have a Flow Velocity Wafeform w a well defined protodiastolic notch.

-End diast flows incr in the main ut arts and their branches in teh 2nd 1/2 of preg, and usually (85% pts) the protodiast notch disappears by 20weeks GA, bc of end of implantation process...,

-blood flows in the spiral arts in preg- see low impedance irregular flow pattern w/o much change thru preg.

-Doppler- see progressive decr in downstream resistance to Q in ut arts thru the pregnancy, seen in all ut arts.

-Reistance Index (RI) aka Pulsatility Index (PI) - measured from teh FVWs recorded at main ut arts- reflects downstream flow impedance of the whole ut circ.

-bn 12-14wk GA, --> rapid incr in pk velocity fr 50 to 120cm/s at ut arts,

-the resistance and pulsatility indices in main ut art twd the spiral arts decreases thru the pregnancy

-likely that there is establishment of a small amt of Q bn mom's ut art and the intervillous space at 2mo GA, and/or gradually established during 3-4th month

Abnormal Uteroplacental Circulation Development

-1/3 of human pregnancies have a placental disorder (!) (includes miscarriage and preeclampsia)

-oxidative stress is key to xx

-in 2/3 of early PG fail, there's anatomic evidence of defective placentation- w thinner and fragmented trophoblast shell, reduced cytotrophoblast invasion, incomplete plugging of spiral artery tips; assoc w absence of changes to the spiral arts--> premature onset of maternal circulation thru the entire placenta…--> oxidative stress, and direct mechanical effect on villous tissue as it is enmeshed in blood thrombi ==> placental degeneration, detachment

-Preeclampsia- similar but less xx in early troph invasion- it's enough to anchor the conceptus but not enough to fully convert the spiral arteries into low resistance channels --> sm muscle in their walls is retained --> vasoreactive in up to 1/2 the placental vasc bed--> decr perfuson of intervillous space, and intermittent perfusion --> transient hypoxias to fetus so low grade ch ischemia-reperfusion injury

-3 stages: excessive maternal immune response--> impair implantation w ch oxidative stress--> diffuse maternal endothelial dysfx

-In Vivo Features of Abnormal Placentation

-abNl placentation --> maternal Q enters intervillous space at greater velocity & pressure ==> inflow appears like a jet stream surrounded w turbulence, enough force to drive apart villous branches and form intervillous lakes = maternal lakes

-If severe, see abNl IVS circ fr start of 2nd Tri--> 'jelly like' placenta; overall decr in placental echogenicity, also see assoc incr in serum alpha fetal protein, and fetal growth restriction early, c/w damage to villous membranes, espec the trophoblastic layer

-see assoc bn incr impedance to flow in ut arts and the dvpmnt of preeclampsia, fetal growth resist, and perinatal death

-…

-premature entry of maternal blood into IVS --> disrupt placental shell …--> abortion

Normal Umbilicoplacental Circulation Development

-fetal vasculature development begins in 3rd week post-conception(5th week of PG)

-the hemangioblastic cell cords form within the villous stromal core

-by start of 4th week post-conception, the cords have lumens and the endothel cells flatten out…

-then neighboring tubes connect into a plexus which will unite w the allantic vessels that dvp in the connecting stalk to -- fetal circulation to the placenta

-at 28 days p ovulation (6 menstrual weeks), the villous vasculature is connected w the primitive heart and the vascular plexus of the yolk sac, via vessels in the connecting stalk

-by 5th week GA end, primitive heart starts to beat, and fr 6-9 weeks GA, there is rapid incr in HR, then plateau at 2nd Tri. Fetoplacental circ is established fr 8th week of gestation

-There is no innervation beyond the prox 1-2cm of umbilical cord, so the umbilicoplacental circ is likely passive circulation, w flow rate d/o perfusion pressure

Villous Circulation Development

-after 25 weeks GA, the terminal capillary loops are made…, are often dilated at the apex of the villi to make sinusoids (? decr resistance, improve distribution of fetal Q through the villous trees). Placental capillary formation finishes in mid gestation. In mature placenta, villous circ is made of a muscularized stem artery branching >10 times and ending in a long capillary loop w perivascular capillary networks.

Umbilicoplacental Circulation Hemodynamics

-in 2nd 1/2 of PG, the lowest resistance is at the placental vasc bed mainly bc of large total area of vasc bed,

-initially bld viscosity is high as Hct increases (later decreases) so higher resistance to Q… but really the vasc bed is still low resistance bc of total area…

-in 2nd Tri, ?mech for lowering resistance further, bc no innervation it must be either local vasorelaxants or fr angiogenesis but the formation of more cap beds is not directly related to the rapid drop in umb art resistance seen bn 12-14 weeks GA…

In Vivo Features of Umbilicoplacental Circulation

-in 1st Tri, umb art has high resistance to Q (reflective of higher placental resistance…)- see narrow systolic waveforms, absence of end diast flow, and high pulsatility index

-at 12-14 weeks GA, end diast flow dvps quickly but is incompletely/inconsistently present

-after a while, the PI gradually decreases until end of 3rd Tri

-In early preg, there's NO relationship bn umb art Doppler impedance indices, fetal HR, or villous angiogenesis

-the appearance of end diast flow and the drop in umb art PI correspond to establishing intervillous circ

-In late preg, there's NO relationship bn umb art restance to Q and fetal Hct or umb cord length