Uteroplacental Lecture 1 Flashcards
What does UBF stand for?
Uterine Blood Flow
What does IUGR stand for?
Intrauterine Growth Restriction
What does PIH stand for?
Pregnancy Induced Hypertension
What does Gravida mean?
of pregnancies
What does Para mean?
of live births or still births >20 weeks
What does P50 mean?
Oxygen level at which Hgb is 50% saturated
What does HbF and HbA stand for?
Fetal Hemoglobin
HbA = Adult Hgb
Uterine perfusion increases or decreases throughout gestation?
Increases
What is uterine blood flow at term?
What percentage of CO is this?
~ 700 ml/min
~ 12% of CO
What is the primary source of uterine blood flow? This is a branch of what arteries?
Uterine Arteries that branch from internal iliac (hypogastric) arteries
What is the secondary source of uterine blood flow?
Ovarian Arteries that branch from the aorta at the L4 level
Where does a majority of the uterine blood flow pass through? What percentage of the UBF passes through here?
Intervillous space sees a majority of UBF
*70-90% of uterine blood flow passes through intervillous space
What is the location and function of the intervillous space?
-Intervillous space is located within the placenta between the mother and fetus.
-It serves as a low resistance area where exchange of gas and nutrients occurs.
Uterine blood flow = __________ ?
Formula for uterine blood flow.
Uterine perfusion pressure ÷ Uterine vascular pressure
Uterine perfusion pressure = __________?
Uterine arterial pressure - uterine venous pressure
Uterine blood flow lacks any mechanism for autoregulation during pregnancy. What are the implications of the lack of UBF regulation?
Uterine blood flow is entirely dependent on maternal blood pressure.
Must treat any HoTN
-especially HoTN secondary to neuraxial anesthesia (sympathectomy)
Uterine blood flow in normal pregnancy exceeds the fetal O2 demand requirements.
What are the overarching causes of decreased UBF?
- ↓ uterine arterial pressure
- ↑ uterine venous pressure
- ↑ uterine vascular resistance
What are three factors that lead to decreased uterine arterial pressure?
-Supine position: due to aortocaval compression
-Hypovolemia: d/t dehydration or bleeding
-HoTN: Neuraxial anesthesia, hemorrhage/EBL, drug-induced
How will neuraxial anesthesia affect UBF in the presence of Hypotension?
Sympathetic blockade → hypotension → decreased uterine arterial pressure = ↓ UBF
How can HoTN be counteracted when placing an epidural?
1 liter Fluid bolus before block to counteract hypotension. This has fallen out of favor
-delaying epidural placement while bolusing fluid
Co-loading (15 mL/kg) of fluid
-proven to be effective
How will supine positioning affect uterine venous pressure?
↑ venous pressure due to IVC compression
How will contractions affect uterine venous pressure?
- Contractions = ↑ venous pressure
UBF inversely r/t contraction strength - Tachysystole (Lots of strong contractions in short term.)
-Hyperemia (excess uterine blood flow) during uterine relaxation
What drugs will cause a tachysystolic (frequent strong uterine contractions) state?
- Oxytocin
- Cocaine/Meth
What factors will increase uterine vascular resistance?
- Endogenous vasocontrictors (catecholamines from stress response)
- Exogenous catecholamines (Phenylephrine & Ephedrine)
Is phenylephrine or ephedrine preferred for parturient patients?
Phenylephrine (vasopressor of choice if multiple doses are needed)
Ephredrine can be used but crosses placental barrier and increases fetal metabolic requirements.
How does neuraxial anesthesia with an epi wash affect UBF?
- No change in healthy patients
epi wash: draw up epi into syringe and squirt it out before drawing up LA
What test dose of epinephrine is used in neuraxial anesthesia for parturient patients? How will this test dose affect UBF?
10 - 15 mcg of epinephrine
This test dose will not change UBF
How do clonidine and precedex affect UBF when administered:
Neuraxially?
Intravenously?
- Neuraxial = No change in UBF
- IV = ↓ UBF d/t ↑ UVR
*may stimulate α₂ receptors in the uterine arteries, causing vasoconstriction and increasing uterine vascular resistance (UVR).
Neuraxial anesthesia will increase UBF if _________ is avoided. What is the mechanism behind this increase in UBF?
Increased UBF if hypotension avoided
-Neuraxial anesthesia will provide pain control which will l/t decreased circulating catecholamines
How do volatile anesthetics affect UBF?
↓ UBF if MAC > 1.5 (obviously rare)
-decreased CO/BP l/t ↓UAP
Minimal effect on UBF with MAC 0.5 - 1.5
The chorionic plate of the placenta originates from the _____ side.
fetal
The basal plate of the placenta is on the _______ side. What is the function of the basal plate?
-Basal plate is the maternal side of the placenta
-Basal plate contains spiral arteries
-These arteries allow blood pool into intervillous space and allows for exchange with fetal capillaries
What are the functions of the placenta?
Functions as endocrine organ
- Production of proteins, hormones, enzymes
- Gas exchange
- Nutrient & waste exchange
Where does the main stem villus extend from and what is its purpose?
Main Stem Villus
- Originates on the fetal side of chorionic plate
- extends down into intervillus space
Function:
- contains fetal capillaries that allow for interaction with maternal blood
What is the intervillous space?
Large placental sinus with multiple folds
-location in placenta where fetal capillaries and maternal blood interact to exchange nutrients and exchange gas.
How much blood is in the intervillous space at one time?
350mls
Where does blood enter the intervillous space?
spiral arteries
-These arteries are always present in uterus
-they embed into placenta shortly after conception
The umbilical vein contains __________ blood. Describe the path of blood flow through the umbilical vein
Umbilical vein contains oxygenated blood
Blood flow of umbilical vein
-umbilical vein delivers oxygenated blood from the maternal circulation to the fetus
The umbilical arteries (two in number) carry ________ blood. Describe the path of blood flow through the umbilical artery?
deoxygenated blood
Umbilical artery
-takes deoxygenated blood from fetus and delivers it to maternal circulation
What variables change the rate and amount of transfer of substances (drugs, toxins, O₂, CO₂, etc.) in the intervillous space?
- Concentration gradient
- Permeability
- Restriction of movement: some substances are bound within placental tissue or bound to proteins which minimizes fetal exposure and accumulation
What substances/drugs move via passive diffusion?
- O₂ (moves down concentration gradient from maternal blood to fetal capillaries)
- CO₂ (moves down concentration gradient from fetal circulation into maternal blood)
- Most anesthetic drugs
What is facilitated diffusion? How does temperature affect the rate of facilitated diffusion?
Facilitated Diffusion: movement with the help of carrier proteins, following a concentration gradient.
-follows saturation kinetics: rate of transfer maxed out when all binding sites are saturated
Higher temperatures will increase rate of transfer
What’s an example of a molecule that moves via facilitated diffusion?
Glucose
What is active transport? What are some characteristics of active transport?
Movement against concentration gradient requiring energy in the form of ATP
- Protein membrane carrier required
- Saturation kinetics
- Competitive inhibition
ex. Na⁺, K⁺, Ca⁺⁺
What transfer mechanism is characterized by membrane rearrangement, vesicle formation, and the movement of large macromolecules?
Pinocytosis
requires energy
What is an example of pinocytosis transfer in pregnancy?
Transfer of IgG from mother to fetus
What are the major factors that impact drug transfer across the placenta?
- Blood flow
- Lipid solubility
- Protein binding
- pKa & pH/charge
- Molecular size
(Also, gestational age, maternal factors, and placental drug metabolism).
What is the primary factor affecting anesthetic drug delivery across the placenta? Why?
Blood flow because most drugs are passively transferred.
need enough blood flow to bring substance to placenta
How does lipid solubility affect drug transfer from mother to fetus?
High lipid solubility of drug l/t increased lipid bilayer penetration
-may encourage drug being trapped in placental tissue
What drug has high lipid solubility resulting in placental tissue trapping of the drug?
Sufentanil
Why are bupivacaine and ropivacaine less likely to cross the placenta?
Both are highly protein-bound.
Albumin binds to _____ and ________ compounds.
acidic & lipophillic
α-1 acid glycoprotein binds to ______ compounds.
basic
What is pKa?
The pH at which 50% of a drug is ionized & 50% is non-ionized
Do ionized or non-ionized drugs tend to cross the placenta more easily?
non-ionized
What is ion-trapping?
The fetus usually has a lower pH (more H+) than the mother.
-Non-ionized drugs can cross placenta easier
-The H+ present in fetal blood bind to non-ioinized drug
-Drug becomes Ionized
-Ionized drug can not cross back to maternal side as easy
-This is considered “ion trapping”
What is an example of a highly ionized drug that doesn’t cross the placenta easily?
- Succinylcholine
Drugs with a molecular weight of ________ typically cross the placenta.
< 500 Da (Daltons)
Most drugs with a molecular weight of _______ do not cross the placenta.
> 1000 Da (Daltons)
What are examples of drugs that don’t cross the placenta due to their high molecular weight?
- ND NMBD’s
- Heparin
- Protamine
What anticholinergics readily cross the placenta?
- Atropine
- Scopolamine
What anti-hypertensives readily cross the placenta?
- β blockers
- Nitroprusside
- Nitroglycerin
What local anesthetic can readily cross the placenta? (in contrast to other LA’s)
Lidocaine
What are some drugs/drug classes that readily cross the placenta?
- VAA’s
- Benzo’s
- Ephedrine
- Induction agents (propofol, ketamine, etomidate, precedex)
- Tylenol
- Neostigmine
- Warfarin
What drugs DO NOT readily cross the placenta?
- Glycopyrrolate
- Heparin (MW too large)
- Succinylcholine (highly ionized)
- Non depolarizing NMBD’s (MW too high)
- Sugammadex*
- Phenylephrine
What drugs should be used to reverse paralysis in pregnant patients? Why?
Neostigmine & Atropine
-Glyco does not cross the placenta but neostigmine does.
Neostigmine with glyco will cause severe fetal bradycardia .
-Atropine crosses placenta and is suitable to prevent fetal and maternal bradycardia with neostigmine.
What is a teratogen?
Substance that increases the risk of a fetal defect that cannot be atrributed to chance
In order to produce a defect, teratogens must be administered in a sufficient dose, during which point in development?
15 - 60 days gestational age
Which anesthetics drugs are proven teratogens?
None
However, we like to minimize or eliminate fetal exposure to anesthesia in the 15 - 60 days gestational period.
What drug that we commonly use is not regulated by the FDA?
N₂O (medical gas, not drug)
What is the teratogenicity profile of benzodiazepines?
GABA has been shown to cause cleft palate formation: Benzos enhance GABA activity in CNS
Diazepam = class D FDA rating (positive evidence of risk)
-Human retrospective studies show association between diazepam in the first 6 weeks of pregnancy and cleft palate formation.
- Chronic exposure (not a one time low dose) in all studies linking diazepam to cleft palate
How does meperidine effect the fetus?
- Neonate CNS depression
- Can cause seizures due to normeperidine accumulation
How does morphine affect the fetus?
- ↓ maternal respirations = ↓ fetus O₂
- fewer fetal heart rate accelerations
-fetal heart rate accelerations are a reassuring sign
What opioid can be really useful for maternal sedation? Why?
Remifentanil: maternal sedation w/o significant neonatal effects
Rapid metabolism = minimal fetal exposure.
What is P50 ?
The partial pressure of O₂ at which Hgb is 50% saturated with O₂
How does the P50 of HbF compare to that of HbA?
HbF = 19 mmHg
HbA = 27 mmHg
HbF will preferentially pick up O₂ from the mother’s blood.
A lower P50 will result in a ________ affinity. Why is this an important concept?
higher
-Fetal blood is a lower O2 environment
-HbF higher O2 affinity/HbA lower O2 affinity allow more O2 to be transferred from maternal circulation to fetal circulation.
What concept describes how oxygen affinity of Hgb is influenced by concentration of CO₂ and pH of surrounding environment?
Bohr Effect
What is meant by a right shift in the Oxyhemoglobin dissociation curve? What factors lead to a right shift?
Right shift means the Hgb will have a decreased affinity for oxygen (higher PO2 needed for 50% O2 saturation)
- enhanced release of oxygen from Hgb
Factors:
↑ H+ ( ↓pH)
↑ CO2
How will maternal hyperventilation affect fetal oxygenation?
Hyperventilation = hypocapnia/maternal alkalosis → maternal oxyhemoglobin curve shifts left and prevents as much O₂ from getting to the baby
What is meant by double-Bohr Effect?
First Bohr effect:
-right shift of maternal arterial Hgb due to increased placental PCO2
Second Bohr effect:
-left shift of HgF due to decreased PCO2 in the umbilical venous blood
What drugs can cause dose dependent decreases in uterine arterial pressure and therefore HoTN?
Dose-dependent
Propofol and volatiles
Opioids
Magnesium
What is the treatment for HoTN?
Vasoconstrictors and fluid bolus
In addition to crossing the placental barrier and increasing fetal metabolic requirements, ephedrine can also cause what unwanted effects?
Ephedrine increases fetal metabolic requirements and has also been shown to:
-decrease fetal pH
-decrease fetal base excess
-decrease umbilical O2 content
How does epinephrine IV affect Uterine blood flow?
Epinephrine IV leads to decreased UBF by increasing uterine vascular resistance.
What two drugs can be given to increase UBF and decrease uterine vascular resistance?
Hydralazine
-direct relaxation of arterioles
Magnesium sulfate
-relaxes smooth muscle
-vasodilation
Note: mag will l/t decreased Uterine arterial pressure (↓ UBF) if it causes HoTN
What structure contains fetal capillaries?
Main stem villus.
-it extends from chorionic plate (fetal side) down into intervillus space.
-Contains fetal capillaries which interact with maternal blood in intervillus space to exchange gas/nutrient.s
Why is the placenta considered a transient organ?
Placenta is an organ that is only present when baby is present
-develops shortly after conception
How does protein binding affect drug transfer from mother to fetus?
Highly protein bound drug transfer is highly dependent on maternal and fetal plasma protein levels.
Highly protein bound drugs have harder time crossing placenta
How can low maternal or fetal plasma protein affect transfer of highly protein bound drugs?
If fetal or maternal proteins low, more unbound drugs in circulation
free, unbound fraction of drug equilibrates across placenta
What are two drugs that are non-ionized and subject to ion trapping?
Lidocaine
Opioids
What opioid can be used for pain relief without significantly affecting fetus?
Butorphanol (Stadol)
-mixed agonist-antagonist both blocks and activates pain receptors
What is meant by a left shift in the Oxyhemoglobin dissociation curve? What factors lead to a left shift?
“left= lock or L for Love”
Left shift is an increased affinity for O2. (P50 achieved at lower PO2)
Fetal blood will uptake more O2 from maternal circulation
Factors:
↓H+ (↑ pH)
↓ CO2
How will maternal hypercapnia affect fetus?
CO2 crosses placenta easily
-if severe can result in fetal acidosis and myocardial depression
