fetal circulation
Factors Affecting Transplacental Drug Transfer - Protein binding- Affected by what two things.? Diazepam bind to ___________; sufentanil binds to ___________. albumin binds primarily _____________ and ___________ compounds whereas AAG binds more ______________ compounds.
Affected by mom and fetal plasma protein. Diazepam bind to albumin; sufentanil binds to AAG. albumin binds primarily acidic and lipophilic compounds whereas AAG binds more basic compounds
Barrier Function of the Placenta- Transfer influenced by 3 things: dmb
Degree of permeability,Membrane thickness,Binding.
Fetal Adaptation / Circulation- Ductus Arteriosus (DA)- Closes in how much time?. Hole b/t __________ and _______; shortcut to the ________; skips _________.
Ductus Arteriosus (DA)- Closes in hours (~24). Hole b/t Pulm Art and Aorta; shortcut to the Aorta; skips lungs
Maternal side - Placental Circulation- ____________ and ___________ arteries supply the uterus (O2). Uteroplacental perfusion originates from where?
Maternal side - Placental Circulation- Uterine and ovarian arteries supply the uterus (O2). Uteroplacental perfusion originates from the uterine and ovarian arteries
Decidua Basal Plate- fetal or Maternal side? Contains _____________ and ________________
Maternal side. Contains spiral arteries and intervillous space
Uterine placental blood flow Pathological conditions (3):
Pregnancy induced hypertension, Diabetes, Post dates
Umbilical Cord- The UV can be used to infuse ___________ and ____________ (UVC). The UA can be used for an __________________ . Blood can be drawn from the ________.
The UA can be used for an arterial line (UAC). Blood can be drawn from the UV or transfused into the vein during intrauterine life for fetal assessment or treatment (percutaneous umbilical blood sampling -PUBS)
Barrier Function of the Placenta-Membrane thickness-Thickness decreases as gestation progresses, which "should" increase what?
Thickness decreases as gestation progresses, which "should" increase the rate of diffusion
Teratogenicity depends on......Greatest risk is when?
Timing, dose, drug, organ. Greatest risk is 15-70 days
Umbilical Cord - Formed from WHAT membranes. Provides a 'circulatory pathway' connecting the embryo to the _______________ of the __________________.
Umbilical Cord - Formed from fetal membranes. Provides a 'circulatory pathway' connecting the embryo to the chorionic villi of the placenta.
Transplacental Drug Transfer- Fetal exposure- determined by what?
determined by placental permeability and pharmacokinetics
Transplacental Drug Transfer -Fetal-Maternal (F/M) Ratio Drug Concentration is influenced by:
drug metabolism in the mom, placenta and fetus, and also by altered uteroplacental blood flow
Factors Affecting Transplacental Drug Transfer- pKa of drug- definition? fetal acidosis does what to transfer?
fraction of a drug non-ionize at physiological pH. fetal acidemia enhances transfer.
Maternal Side-Placenta Circulation- 200 Spiral arteries: directly feed the fetus by gaining access into the _________________.
intervillous space
Uterine Blood Flow equation
uterine arterial pressure- uterine venous pressure/ uterine vascular resistance
Major Placental Structures- Chorion Plate- maternal or Fetal side? Contains branches of what vessels?
fetal side . Contains branches of umbilical vessels
Factors Affecting Transplacental Drug Transfer- Size: how does lower molecular wgt. effect transfer?
lower molecular wgt. increase transfer
Placental Transfer: I.V. Agents- Muscle Relaxants- Are highly ionized which impedes placental transfer, resulting in ......
minimal effects on the fetus
Fetal Circulation Pathway
mom to placenta to uv to dv to fo to da to ua
Barrier Function of the Placenta- true /false...Almost all substances pass thru placenta
true
Anything that Decreases uterine arterial pressure, Increases uterine venous pressure and Increases uterine vascular resistance will have what effect on u/p blood flow?
will DECREASE Uteroplacental (U/P) BlOOD FLOW
Fetus relies on placenta for: WON
-Oxygen (Gas exchange), Nutrients,Waste removal (CO2)
Fetal Adaptation / Circulation- Foramen Ovale (FO)- Closes in _____________. Hole b/t what two places? provides shortcut to what two places?.; skips what area?
. Closes in minutes. Hole b/t R and L Atrium; shortcut to the L Atrium and Pulm. Arts.; skips R vent
Etomidate-A dose of_______ to ________ mg/kg administered for cesarean delivery resulted in an F/M ratio of approximately _______. 3,4,5.
.A dose of 0.3 to 0.4 mg/kg administered for cesarean delivery resulted in an F/M ratio of approximately 0.5
Amniotic Fluid- does it changes as baby grows? function? provides valuable information for what?
A complex fluid, changes as pregnancy progresses and the fetus develops. Facilitates fetal growth. Cushions the fetus with a microgravity environment. Generates defense mechanism against invading microbes. Provides valuable information on chromosomal abnormalities, defects, prenatal infections
FDA Drug Categories
Category A no risk to reproduction, Category B C D increasing risks, Category X should not be used in pregnant women or women of reproductive age who are not on BC
Chorion - WHAT layer? Contains no _____________ or _______________. THINNER OR Thicker than amnion?
Chorion - outer layer. Contains no vessels or nerves. Thicker than amnion
Fetal Adaptation / Circulation- Ductus Venosus (DV)- closes when? Comes off ________; shortcut to the _______; skips circulation where?
Closes in days. Comes off UV; shortcut to the IVC; skips circulation in the liver
Placenta - Complex organ, attached to the ______________ _____________, and connected to the fetus via the ________________ _________________.
Complex organ, attached to the uterine wall and connected to the fetus via the umbilical cord
Utero/Placental Blood Flow- Affected by:
Contractions, Decreased maternal MAP, Drugs, Maternal hypocapnia,
WHATS "Wharton's jelly"?
Cord is gelatinous filled with "Wharton's jelly", prevents pressure on the UA and UV
FDA Categories and Adverse Fetal Effects for decadron, warfarin, edrophonium, atenololand benzos
Decadron-cleft lip before 10 weeks (C) Warfarin-spontaneous abortion, defects of face, brain & eyes. Edrophonium- preterm labor (C) Atenolol- low birth weight infants (D). Benzo- cleft palate (D)
Postnatal circulation is characterized by increase/decrease in pvr? pulm. blood flow?svr?la pressure?
Decreased PVR, Increased pulmonary blood flow, Increased SVR, Increased LA pressure
Amnion -WHAT layerS . FXN? Produces .......
Amnion - inner layer . Support to the amniotic fluid; produces the fluid. Produces phospholipid that initiates formation of PGE.
Fetal Membranes (Fetal Sac) Consist of two Layers:
Amnion - inner layer, Chorion - outer layer
Persistent Fetal Circulation Causes:
Anything that precipitates pulmonary vascular constriction. Hypercarbia,Hypoxia, Acidosis
Maternal Side-Placenta Circulation- Intervillous space: filled with what? btw what two structures? allows for......... is intervillous space pressure lower or higher than fetal side? why? what is intervillous space pressure during relaxation and contraction?
Blood filled space "maternal blood lake" b/t the chorion and basal plates. Allows for efficient exchange of substances b/w mother & fetus. Intervillous space pressure is lower than fetal side d/t dilation. 10-15 mm Hg during uterine relaxation. 30-50 mm Hg during uterine contraction
Transplacental Transfer of Anesthetic Drugs: Drugs that DO NOT Readily Cross the Placenta
Glycopyrolate, Anticoagulants, Heparin, Muscle relaxants, succinylcholine, Nondepolarizing agents, Phenylephrine
Shunts: Which way? how can we tell?
It is important to be able to identify whether a newborn has a right to left shunt or a left to right shunt. If there is any indication that the newborn has reverted to fetal circulation [ie: the newborn is hypercarbic, hypoxic, acidotic] then the shunt is more than likely a right to left shunt.
what makes placenta develop/grow at different stages? placenta is fully developed by when?
Placenta develops as the needs of the embryo outweigh its ability to gain oxygen and nutrients by simple diffusion.Placenta is fully developed by 20 weeks gestation! Placenta enlarges later on d/t proliferation of villus branching placenta weighs ~500 grams at term
Transplacental Drug Transfer- No good human studies done.why?
Placenta inaccessible, Maternal fetal safety concerns
Placenta.usually implants where?
Placenta.usually implants in upper uterine segment
Fetal CO2 Elimination- CO2 diffuses easily. ________ maternal CO2 → uterine & umbilical vessel _____________ →_______________ placental perfusion. Maternal alkalosis shifts fetal curve to the _____________ →_____________ 02 released at placental level. Maternal hypocapnia → fetal ____________ &__________________.
↓ maternal CO2 → uterine & umbilical vessel vasoconstriction →↓ placental perfusion. Maternal alkalosis shifts fetal curve to left →↓ 02 released at placental level. Maternal hypocapnia → fetal hypoxia & acidosis
Basic Function of the Placenta
**Links maternal & fetal circulation, Massive exchange and transfer of substances, nutrients, O2, protective antibodies from maternal circulation to fetus. Removes waste products (CO2, urea, uric acid, creatinine) from fetus back to maternal circulation for excretion by her lungs and kidneys.Produces pregnancy hormones (estrogen, progesterone and human chorionic gonadotropin (HCG) hormones make changes in mothers body to accommodate pregnancy and breastfeeding , Barrier Function
PFO- FO is a hole between the ______________ and _____________with a small flap that can fully cover the passage of blood. When the pressure is higher in the ________ the flow will go from __________ to ___________, into the left atrium (This is the second cardiac shunt). When the pressure becomes higher in the left atrium (after birth) ............. If the flap is missing the baby will have a .......................
.FO is a hole between the R and L atrium with a small flap that can fully cover the passage of blood. When the pressure is higher in the RA the flow will go from right to left, into the left atrium (This is the second cardiac shunt). When the pressure becomes higher in the left atrium (after birth) the flap will be forced to close the hole. If the flap is missing the baby will have a patent Foramen Ovale (PFO)
Uterine Blood Flow (UBF)- 3 main factors that diminish UBF:
1. maternal hypotension 2. uterine vasoconstriction 3. uterine contractions
Uterine Blood Flow- what % of co? how many ml/min before conception/at term? 90% of co perfuses what? 10 % perfuses what? is it autoregulated?why or why not?
10-12% of cardiac output. Before conception 50-190 mL/min. Term 700-900 mL/min. 90% perfuses intervillous space (for exchange of substance to occur). 10% perfuses myometrium. Uterine autoregulation is absent in pregnancy due to maximal dilation of uterine vasculature
Umbilical Blood Flow-_______-___________ mL/min at term. Can calculate using.........
120-360 mL/min at term. Can calculate using doppler techniques
Fetal Side- Placental Circulation- Villi: Elongated protrusions of _____________ tissue. Have many branches with a large surface area for ______________. Project into the ________________ _______________ of placenta, pass through the space and anchor onto the ___________ _________. Fetal capillary pressure in villi =________-________ mm Hg
Elongated protrusions of fetal tissue. Have many branches with a large surface area for absorption. Project into the intervillous space of placenta, pass through the space and anchor onto the basal plate. Fetal capillary pressure in villi =20-40 mm Hg
FETAL TYPICALLY CONTAINS how much of THE AAG compared to MOM? Fetal pH is typically _____________? when baby is stress or crash C-section is done babys pH is likely lower which effects drug transfer how?
FETAL TYPICALLY CONTAINS LESS THAN HALF THE AAG OF MOM. Fetal pH is typically low 7.25; when baby is stress or crash C-section is done babys pH is likely lower enhancing drug transfer
Fetal Oxygenation-Fetal PaO2 is _______-_______ mm Hg. How does this compare to the adults? P50 of fetal blood is _______-_________. moms is ______. fetus have higher art of what kind of Hgb .
Fetal PaO2 20-30 mm Hg, and exist in relative state of hypoxia compared with adult O2 tension. P50 of fetal blood is 19-20 mom is 27. Higher Hgb F
Placenta - the fetal life line Comprised of maternal and fetal tissues. fetal primary component, maternal primary component?
Fetal- chorionic frondosum (primary component) Maternal- decidua basalis (plate)
PFO-fo remains open how long? what ind of shunt? what problems could this lead to? why?
Foramen Ovale remains open. Left-to-Right Shunt. Left Ventricle must work harder which could lead to pulmonary hypertension, pulmonary edema and cardiac enlargement
2 Umbilical Arteries- FROM WHERE TO WHERE. LOW in?Carries.....
From fetus to placenta. Low in oxygen. Carries deoxygenated blood and waste to placenta
Umbilical Cord Blood Supply - 1 Umbilical Vein FROM WHERE TO WHERE. High in?Carries..... w/in 1 week, vein becomes _______________ and becomes WHAT VEIN?
From placenta to fetus.High in oxygen.Carries oxygen and nutrient rich blood to fetus. w/in 1 week, vein becomes fibrous and becomes the round ligament in the liver
Fetal Kidneys- Functional in___________ trimester. urine quality?. how many mL/day? Major source of what?
Functional in 2nd trimester. Dilute hypotonic urine. 400-1200 mL/day. Major source of amniotic fluid
Transplacental Transfer of Anesthetic Drugs: Drugs that Readily Cross the Placenta
Halothane, Isoflurane, Sevoflurane, Desflurane*,Nitrous oxide, Local anesthetics, Opioids, Ephedrine,Atropine, Scopolamine, Beta-adrenergic receptor antagonists, Nitroprusside, Nitroglycerin, Benzodiazepines, Diazepam, Midazolam, Propofol, Ketamine, Etomidate, Thiopental
PDA- High Fetal _______________ causes minimal blood flow through the ______________, and __________ is low, making it easy for the blood to flow through the systemic vasculature. This low SVR is beneficial for the unborn baby's heart, decreasing the work required, hence low ___________. The DA is needed in the unborn baby to bypass the pulmonary circulation as there is no benefit for the blood to pass through the lungs for oxygenation (this is the first cardiac shunt). most of the blood leaving the right side of the heart is shunted back to the left side in order to .......... If the ductus arteriosus does not close after birth it is a ...............
High Fetal PVR causes minimal blood flow through the lungs, and SVR is low, making it easy for the blood to flow through the systemic vasculature. This low SVR is beneficial for the unborn baby's heart, decreasing the work required, hence low LAP. The DA is needed in the unborn baby to bypass the pulmonary circulation as there is no benefit for the blood to pass through the lungs for oxygenation (this is the first cardiac shunt). most of the blood leaving the right side of the heart is shunted back to the left side in order to bypass the pulmonary circulation. If the ductus arteriosus does not close after birth it is a patent ductus arteriosus (PDA)
Factors Affecting Transplacental Drug Transfer-Lipid solubility- High lipid sol. may enable transfer but may also cause _____________. example?
High lipid sol. may enable transfer but may also cause trapping (sufentanil)
how does protein binding effect the diffusion across the placenta of bupi compared to ropi compared to lidocaine?
Highly protein-bound agents diffuse poorly across the placenta; thus, greater protein binding of bupivacaine and ropivacaine, compared with that of lidocaine, likely accounts for their lower fetal blood levels.
Placental Transfer: I.V. Induction Agents Propofol- May have sedative effects on the neonate if >_________mg/kg bolus given to mom. 2mg/kg results in F/M ratio of .______?
I.V. Induction Agents Propofol- May have sedative effects on the neonate if >2.5 mg/kg bolus given to mom. 2mg/kg results in F/M ratio .65
IS THE PLACENTA PERFECT?
Imperfect- allows many substances to cross back and forth
Persistent Fetal Circulation what happens physiologically?
Increased PVR = RAP to exceed LAP causing the FO to open and divert deoxygenated blood directly to the left side of the heart (R to L shunt)= HYPOXIA= increased PVR (vicious cycle)
Fetal and Post-Natal Circulation- Fetal circulation is characterized by......increase/decrease in pvr? pulm. blood flow?svr?la pressure? shunt?
Increased PVR, Decreased pulmonary blood flow, Decreased SVR, Decreased LA pressure, R to L blood flow via PDA and Foramen Ovale
Factors affecting propofol placental transfer
Increased maternal blood flow and reduced protein binding increase both placental tissue uptake and transplacental transfer of propofol.Propofol is highly protein bound to albumin. altered albumin concentrations in mom or fetus will affect transplacental transfer
Transplacental Drug Transfer -Fetal-Maternal (F/M) Ratio Drug Concentration - tells us what?. High F/M ratios suggest ..............Single measurement in maternal and cord blood at delivery. Umb. Vein blood. concentration equals what?
Is the degree of fetal exposure to drugs. High F/M ratios suggest the drug is freely diffusible.Single measurement in maternal and cord blood at delivery. Umb. Vein blood concentration = fetal drug concentration
Placental Transfer: Local Anesthetic Agents- LA are weakly ______________ drugs and principally bind to _______________. Placental transfer depends on three factors:
LA are weakly basic drugs and principally bind to alpha 1-acid glycoprotein. factors: (1) pKa (The lower the pKa, the quicker the onset) .(2) maternal and fetal pH (fetal acidosis [and maternal alkalosis] causes fetal ion trapping). (3) degree of protein binding (the higher the protein binding, the lower the transfer to fetus).
Amniotic Fluid: Origin? maternal or fetal. 3 contributing factors?
Mixed maternal and fetal origin. A. Transudate across the umbilical cord or from fetal circulation in the placenta or secretion from the amniotic epithelium B. Transudate of fetal plasma through the highly permeable fetal skin before it is keratinized at 20th week C. Contribution from the fetus- Fetal daily urine output at term is ~400-1200 ml. The fetus swallows about 200-500 ml of "liquor" qd.
PDA- more common in? remains open until? shunt?
More common in premies. Ductus arteriosus remains open post-delivery. Left-to-Right Shunt. Left ventricular hypertrophy, pulmonary hypertension, right ventricular hypertension
Barrier Function of the Placenta- degree of permeability- More permeable when? Less permeable when?
More permeable during early pregnancy. Less permeable to larger sized molecules
Fetal Oxygenation- Oxygen for what?. Dissolved O2 diffuses thru ......... Bound maternal O2 released into ........
Oxygen for growth & development. Placenta uses O2 also. Dissolved O2 diffuses thru placenta. Bound maternal O2 released into IVS
Transport Mechanisms across the Placenta (4) other factors (4):
Passive transport,Facilitated transport, Active transport, Pinocytosis. Other factors: Blood flows (maternal/fetal), Placental binding, Gestational age (early gestation crosses easier), Degree of protein binding both sides
CAN THE AMNION AND CHORION BE SEPERATED?
The layers can be separated
Placental Transfer: I.V. Induction Agents- Ketamine- crosses the placenta? Ketamine 2 mg/kg reached a mean F/M ratio of ____________ in as little as 97 seconds when administered to the mother for vaginal.
Rapidly crosses the placenta. Ketamine 2 mg/kg reached a mean F/M ratio of 1.26 in as little as 97 seconds when administered to the mother for vaginal
Placental Transfer: I.V. Agents- Opiates- cross the placenta? effects on neonates at delivery? ___________ produces the most respiratory depression, ___________the least. Remifentanil also readily crosses the placenta and has the potential to produce respiratory depression in who? why not in the neonate? Epidural or intrathecal opiates to a lesser extent, generally produce minimal _____________ effects.
Readily cross the placenta, but their effects on neonates at delivery vary considerably.Morphine produces the most respiratory depression, fentanyl the least. Remifentanil also readily crosses the placenta and has the potential to produce respiratory depression in newborns. There is fairly rapid metabolism of remifentanil in the neonate. Epidural or intrathecal opiates to a lesser extent, generally produce minimal neonatal effects
Fetal Adaptation / Circulation -Umbilical Artery (UA)- Closes in how much time? fxn? Closes in hours.
Returns mixed blood from fetus back to placenta
Maternal side - Placental Circulation- Spiral arteries 'temporarily' supply blood to the _________________, and nutrients to ___________ and _____________. During pregnancy, the arteries convert into what? d/t what? why? what is blood flow in 3rd trimester? (high or low fetal demand?).
Spiral arteries 'temporarily' supply blood to the endometrium, and nutrients to placenta and fetus. During pregnancy, the arteries convert into highly dilated vessels; d/t inc. blood volume in pregnancy and to inc. uteroplacental blood flow.blood flow-600mL/min in 3rd trimester= (high fetal demand)
Factors Affecting Transplacental Drug Transfer-blpps-
blood flow, lipid solubility, protein binding, pka of drug, size.
Fetal Side- Placental Circulation- Chorionic Arteries: Supply 50 ___________ _________; pass toward _____________ _______________, they branch and divide to _____________ arteries.Embed in large capillary ___________________- allows for ........................ Venous end of capillary, loops and returns to larger veins in __________ _____________. All ____________ tributaries course to the _______________ ______________ which delivers blood back to the fetus.
Supply 50 villous trees; pass toward maternal plate, they branch and divide to terminal arteries.Embed in large capillary endothelium- allows for optimal maternal-fetal exchange. Venous end of capillary, loops and returns to larger veins in villous trees. All venous tributaries course to the umbilical cord which delivers blood back to the fetus.
The ductus arteriosus is a small vessel between the ____________ and the ____________artery. It is needed in the unborn baby to shunt blood that leaves the ___________ side of the heart back to the____________ side, since there is no benefit for the blood to pass through the lungs for oxygenation. Therefore most of the blood leaving the right side of the heart is shunted back to the left side in order to bypass the _________________ circulation. This is the first cardiac shunt.
The ductus arteriosus is a small vessel between the aorta and the pulmonary artery. It is needed in the unborn baby to shunt blood that leaves the right side of the heart back to the left side, since there is no benefit for the blood to pass through the lungs for oxygenation. Therefore most of the blood leaving the right side of the heart is shunted back to the left side in order to bypass the pulmonary circulation. This is the first cardiac shunt
Placental Transfer:Inhalation Agents- The lipid solubility and low molecular weight of inhalation anesthetic agents has what effect on transfer across the placenta? A prolonged induction-to-delivery interval effects Apgar scores how?. Inhalational agents cause little fetal depression under what circumstances? Does Nitrous oxide crosses the placenta?
The lipid solubility and low molecular weight of inhalation anesthetic agents facilitate rapid transfer across the placenta. A prolonged induction-to-delivery interval results in lower Apgar scores. Inhalational agents cause little fetal depression when they are given in limited doses (< 1 MAC) and delivery occurs within 10 min of the induction of anesthesia. Nitrous oxide also rapidly crosses the placenta,
Umbilical Cord Role:
Umbilical Cord Role: transport O2 and nutrients to the fetus from the placenta and return waste products from the fetus to the placenta
Fetal Adaptation / Circulation- Umbilical Vein (UV)- Closes in ___________. UV is the only major source of O2 to where?.
Umbilical Vein (UV)- Closes in days. UV is the only major source of O2 to the fetus (from placenta)
Transition of Circulation: Baby's First Breaths During labor fluids start to reabsorb. Vag delivery =_________________ of baby = expels fluid from lungs= Lungs expand, fill with air, ___________________ released.↑ _______, ↑ _________ = pulmonary ______________ & ↓ ______________. Clamping cord = ↑_________, ↑ _________. Theses events = increased blood flow through the lungs, resulting dec. ________ and inc. ________; ultimately = diminished flow via and functional closure of ______________ & ______________.
Vag delivery =compression of baby = expels fluid from lungs= Lungs expand, fill with air, surfactant released.↑ O2 , ↑ NO = pulmonary vasodilation & ↓ PVR. Clamping cord ↑SVR, ↑ LAP. Theses events increased blood flow through the lungs, resulting dec. RAP and inc. LAP; ultimately diminished flow via and functional closure of ductus arteriosus & foramen ovale
Factors Affecting Transplacental Drug Transfer- Blood flow - blood flow rate affects.....
amt. of drug crossing placenta
Chloroprocaine has the least placental transfer why?
because it is rapidly broken down by plasma cholinesterase in the maternal circulation.
