Exam 2: Uteroplacental & Fetal Physiology Pt. 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?
number of pregnancies
What does Para mean?
of live births or >20 weeks
What does P50 mean?
Oxygen level at which Hgb is 50% saturated
What does HbF 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 of mom
Pregnancy is ____ resistance, but _____ flow.
Low Resistance, High Flow
Vasodilation w/ ↑ volume & CO
What is the primary source of uterine blood flow?
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
70 - 90% of uterine blood flow will pass through the ____ space.
Intervillous space
Low resistance area of maternal blood pooling for exchange of gas nutrients.
Uterine blood flow = __________ ?
Formula for uterine blood flow.
Uterine perfusion pressure ÷ Uterine vascular resistance
Uterine perfusion pressure = __________?
Formula
Uterine arterial pressure - uterine venous pressure
What is the mechanism for autoregulation of UBF during pregnancy?
Trick question. There is no autoregulation of UBF. Entirely dependent on maternal blood pressure.
Is there “wiggle room” for maternal blood pressure when it comes to uterine prefusion?
Yes, there is wiggle room
- in a normal healthy mother, the UBF exceeds the minimal demand for fetal oxygen
What are the overarching causes of decreased UBF?
- ↓ uterine arterial pressure
- ↑ uterine venous pressure
- ↑ uterine vascular resistance
What position would compromise uterine arterial pressure?
Supine due to aortocaval compression
Hypovolemia (dehydration/bleeding) will result in decreased ____ and thus decreased UBF.
decreased uterine arterial pressure
How will neuraxial anesthesia affect UBF?
Sympathetic blockade → hypotension → decreased uterine arterial pressure = ↓ UBF
glive fluid bolus either before or during the procedure (research shows coloading is best)
How will supine positioning affect uterine venous pressure?
↑ venous pressure due to IVC compression
How will contractions effect uterine venous pressure?
- Contractions = ↑ venous pressure (UBF inversley related to contraction strength)
- Tachysystole (Lots of strong contractions in short term.)
- Hyperemia during urterin relaxation (squeezes blood out, then blood comes back in when it relaxes)
What drugs will cause a tachysystolic state?
- Oxytocin
- Cocaine/Meth
What occurs with uterine blood flow during uterine relaxation? (such as after a contraction)
Hyperemia (increased blood flow)
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?
Both are effective but:
- Phenylephrine is best if repeated doses are needed
- Ephredrine can be used but crosses placental barrier and increases fetal metabolic requirements.
High concentrations of local anesthetics will have what effect on uterine blood flow?
↓ UBF from high LA’s from:
- Arterial constriction
- Inhibition of endothelial vasodilation
- Stimulation of myometrial contraction
How does epinephrine, administered neuraxially, affect UBF?
- No change in healthy patients
What test dose of epinephrine is used in neuraxial anesthesia for parturient patients?
10 - 15 mcg
How do clonidine and precedex affect UBF when administered:
Neuraxially?
Intravenously?
- Neuraxial = No change in UBF
- IV = ↓ UBF
Neuraxial anesthesia will increase UBF if ____ is avoided.
hypotension
How do volatile anesthetics affect UBF?
↓ UBF if MAC > 1.5 (obviously rare)
Minimal effect on UBF with MAC 0.5 - 1.5
normal MAC range will be fine with CO
How do magnegium and Hydralazine effect UBF?
- Magnesium: increases UBF, relaxes smooth muscles, and causes vasodilation (all dose dependent)
- Hydralazine: increases UBF, direct relaxation of arterioles (all dose dependent)
if we have HoTN from these, then it decreases UBF - dose dependent
B/C of decreased UVR (uterine vascular resistanct)
The chorionic plate of the placenta faces the ____.
fetus
The basal plate of the placenta faces the ____.
mother
What are the functions of the placenta?
- Production of proteins, hormones, enzymes
- Gas exchange
- Nutrient & waste exchange
drug and toxin transfer can occur
What is the intervillous space?
Large placental sinus with multiple folds
The intervillous space is a high resistance area. T/F?
False. The intervillous space is a low resistance area.
How much blood is in the intervillous space at one time?
350mls (70-90% of blood flow to the uterus is pooling in the intervillous space)
Where does blood enter into the intervillous space from?
spiral arteries
The umbilical vein carries ____ blood.
oxygenated
The umbilical arteries (two in number) carry ____ blood.
deoxygenated
What variables change the rate and amount of transfer of (drugs, toxins, O₂, CO₂, etc.) in the intervillous space?
- Concentration gradient
- Permeability
- Restriction of movement (some substances are bound to in the placental tissue to prevent fetal uptake)
What substances/drugs move via passive diffusion?
- O₂ from mom to placenta
- CO₂ from placenta to mom
- Most anesthetic drugs
In regards to facilitated diffusion, a higher temperature will ____ rate of diffusion.
increase
What’s an example of a molecule that moves via facilitated diffusion?
Glucose
Active transport requires ____.
What is required for active transport?
ATP
- Protein membrane carrier
- Saturation kinetic principle applies still
- Competitive inhibition
ex. Na⁺, K⁺, Ca⁺⁺
What transfer mechanism is characterized by membrane rearrangement, vesicle formation, and the movement of large macromolecules?
Pinocytosis
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 (high to low concentration).
High lipid solubility results in ____ bilayer penetration.
more
but may encourage drug to become trapped in the placental tissue
What drug is an example of 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.
Highly protein bound drugs have a harder time crossing the placenta
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 than the mother resulting in drugs being trapped in fetal circulation via H⁺ binding to non-ionized drug.
The then ionization of the drug cannot cross back over into the maternal circulation
What is an example of a non-ionized drug that can frequently get “trapped” in the fetal circualtion?
Lidocaine: non-ionized, but becomes ionized when it crosses into fetal circulation. The ionized drug cannot cross the lipid membrane to get back to the maternal circulation
What are examples of highly ionized drugs that don’t cross the placenta easily?
- LA’s
- Opioids
- Succinylcholine
Drugs with a molecular weight of ____ typically cross the placenta easily.
< 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 induction agents can cross the placenta?
- Propofol
- Ketamine
- Etomidate
- Dexmetatomadine
What drug classes typically are able to readily cross the placenta?
- Anticholinergics
- Anti-hypertensives
- VAA’s
- Benzo’s
- Ephedrine
- Induction agents
- Tylenol
- Neostigmine
- Warfarin
What drugs DO NOT readily cross the placenta?
- Glycopyrrolate
- Heparin (too large)
- Succinylcholine (charged)
- NDNMBD’s
- Sugammadex*
- Phenylephrine
What drugs should be used to reverse paralysis in pregnant patients? Why?
Neostigmine & Atropine
Glyco does not cross the placenta, thus neostigmine will cause severe fetal bradycardia in conjunction with neostigmine. Use atropine to avoid this.
How much should you change your dose of sugammadex when giving to a pregnant pt?
Trick question.
Administration of sugammadex to pregnant pts is not reccommended because it has not been widly studied
- but we do know sugammadex can be detrimental to someone in the first trimester becasue it can bind to and encapsulate pregnancy hormones
What is a teratogen?
Substance that increases the risk of a fetal defect
When during development are teratogens most likely to cause fetal defect?
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)
considered harmful to DNA synthesis in animals in high doses
What is the teratogenicity profile of benzodiazepines?
- Probable cleft palate formation from GABA activity
- Chronic exposure (not a one time low dose)
Especially Diazepam (class D rating).
only retrospective studies and only chronic administration of benzos
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
What opioid can be really useful for maternal sedation? Why?
Remifentanil
Rapid metabolism = minimal fetal exposure.
Butorphenol (stadol) and the effect on the fetus
- mixed opioid agonist-antagonist both block and activate pain receptors
- can be useful for pain relief without as much side effects to fetus
What is P50 ?
The partial pressure of O₂ at which Hgb is 50% saturated with O₂
This helps us quantify the affinity of hgb for O2.
At ____ mmHg of partial pressure of oxygen, 50% of fetal hgb are saturated.
19mmHg
What is the P50 of adult Hgb?
27 mmHg PO2
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.
HbF has a higher affinity for O2 than an adults affinity
A lower P50 will result in a ________ affinity.
higher
What concept is linked with the increase of CO₂ and decrease of pH resulting in a ____ affinity of Hgb for oxygen.
Bohr Effect
decreased affinity
The presence of CO₂ and blood acidity in fetal blood will ____ the release of of O₂ from maternal hemoglobin.
enhance
Right shift = Release
What happens as the CO₂ content of fetal blood decreases?
Fetal blood becomes alkaline compared to maternal blood → curve shifts left → facilitates more O₂ uptake by HbF (increased affinity).
Left shift = Lock
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
How will maternal hypoventilation affect the fetal oxygenation?
Hypoventilation = maternal hypercapnia
- CO2 readily crosses the placenta: if its severe, it can result in fetal acidosis and myocardial depression
