Placental physiology + amniotic fluid Flashcards
Placental metabolism
not passive
rapid growth in first trimester, size >fetus for 16 weeks
decreased growth rate during later pregnancy but extensive maturation - increased branching, decreased thickness, functionally increased surface area
Blood/energy supply to placenta via maternal uterine artery
Placenta uses more energy than fetus (1/2 O and 2/3 glucose delivered to uterus)
Synthesizes glycogen
Produces proteins/steroids
Active transport of some elements
Concurrent blood flow in placenta
maternal + fetal blood flow in the same direction
Both enter in arteries, both leave in veins (parallel transport)
Hemochorial placentation
fetal blood within chorionic villi
Villi bathed in maternal blood
Maternal blood propelled into intervillous space in jetlike streams travelling towards chorionci plate
Blood then percolates down around villi to maternal venous drainage
Gas exchange at the placenta
placental barrier highly permeable to oxygen and CO2
Rate, volume and pressure of blood flow to placenta is major rate determining factor
Maternal:fetal partial pressure also important
Maternal and fetal hemoglobin O2 affinity also important
Simple diffusion in placenta
common for substances with: - large gradient between mom and fetus - LMW - minimal electronic charge - high lipid solubility generally - O2, CO2, H2O
Facilitated diffusion in placenta
Glucose
Main fetal nutrient
Placenta doesn’t produce glucose until late gestation, so uptake of maternal glucose is essential
favourable gradient from mother to fetus
Facilitated diffusion with glucose receptors on placenta
- non-energy dependent, non-insulin dependent
- even more efficient than simple diffusion alone at ensuring adequate glucose supply to fetus
Pregnancy: relative insulin resistance –> increases glucose availability to fetus
Active transport in placenta
Amino acids:
- work against gradient
Lactate:
- large amounts of lactate produced by placental metabolism are transferred to maternal circulation by active transport
Endocytosis in placenta
IgG transfer
- very large
- no concentration gradient
- picked up by receptors at placental barrier
- IgG can also work against us - Rhesus hemolysis etc
Viruses
- likely that some viruses transfer to fetus
Leakage at placenta
Disruption in feto-maternal barrier
Occurs in normal pregnancies in small amount due to microtears at syncytiotrophoblastic barrier
Significant disruption/transfer can occur with abruptio placenta –> massive fetomaternal hemorrhage and fetal anemia/death
Ketone transfer at placenta
- used by fetus when glucose is low
- liposoluble, can cross by simple diffusion
Free FA transfer at placenta
- also used by fetus for energy when low glucose supply (starvation)
- some too large to cross
- essential FFA will cross slowly by simple diffusion
- possibly also some endocytosis
Drug transfer across placenta
depends on: size, charge, gradient, degree of drug protein binding, liposolubility
Many drugs cross in some amount, mostly by simple diffusion
Liposoluble drugs rapidly cross placenta - e.g. inhalational anesthetics
Large drug molecules will not cross (heparin, thyroxin replacement, insulin)
hCG
glycoprotein very similar to LH (same alpha subunit as LH, FSH, TSH; beta subunit unique but similar to LH)
produced almost exclusively by syncytiotrophoblast
Detectable in blood 8-9 d post-ovulation (blastocyst implantation)
Serum level doubles every 48 h, peak at 10 weeks, declines then plateaus
–> useful in following early pregnancy in patients with risk factors/complications
Actions of hCG
rescue/maintenance of corpus luteum (therefore progesterone production)
6 weeks: placenta takes over progesterone production
stimulates fetal testis production of testosterone
hPL
human placental lactogen
Produced by syncytiotrophoblasts (not exclusively)
proportional to placental mass
- production rises steadily until 34-36 weeks
- twins have higher hPL
Actions:
- supports nutritional needs of fetus
- fail-safe mechanism to ensure adequate nutrient supply to fetus especially in fasting state
hPL - maternal fasting state
lipolysis –> increased FFA (maternal energy) and ketones (fetal nutrition)
hPL - maternal fed state
anti-insulin
increased FFA interferes with insulin-directed entry of glucose into cells –> higher circulating glucose –> favours glucose transport to fetus –> gestational diabetes
Gestational diabetes
3-10% of all pregnancies
CH intolerance of variable severity with first onset/recognition during pregnancy
increased in twins due to higher hPL
Progesterone production during pregnancy
From maternal cholesterole
initially by corpus luteum
hCG rescue of CL ensures progesterone production by CL until 6-10 wks
Placental production of progesterone takes over at 6-10 weeks
Also some production by decidua and fetal membranes
Progesterone action during pregnancy
role in endometrial preparation/implantation
Maintain uterine quiescence during pregnancy “pro-gestation”
smooth muscle relaxation of uterus
inhibits uterine PG production (delays cervical ripening)
immunological modulation
Placental progesterone is pool of substrate for production of fetal adrenal corticosteroids
Estrogen production during pregnancy
from maternal androgens (in early pregnancy)
fetal androgens (later pregnancy)
by placenta
Estrogen action during pregnancy
increased uterine blood flow/CO
- peripheral v/d-
- regulates blood volume by stimulation of RAS
Uterine preparation for labour
Uterine contraction in labour
prepares breast for lactation
increase liver production of hormone-binding globulins
Corticosteroid production during pregnancy
by fetal adrenals from placental progesterone
Corticosteroid action during pregnancy
promotes fetal lung maturation
maternal fluid expansion (to fill estrogen-vasodilated vessels)
Amniotic fluid function
vital to fetal survival cushions from trauma prevents compression of umbilical cord allows room for fetus to grow and move - important for limb development and critical for fetal lugn development Bacteriostatic Temperature homeostasis
1st trimester amniotic fluid
initial AF is isotonic with maternal blood
likely derived from transudate of maternal and fetal plasma
- transmembranous: exchange between maternal compartment and fetal compartment
- intramembranous: exchange from one fetal component to another (across unkeratinized fetal skin to amniotic fluid, across fetal surface of placenta to amniotic fluid)
2nd trimester fetal skin keratinized - impermeable
Small volume ~50 ml by 12 wks
2nd/3rd trimester amniotic fluid
balance between production/resorption
Production: fetal urine, lung liquid
Resorption: fetal swallowing, intramembranous pathway
Amniotic fluid production from urine
main component of 2nd/3rd trimester amniotic fluid (>90%)
Fetal kidneys relatively immature in concentrating ability, so fetal urine relatively hypotonic, creating hypotonic amniotic fluid
Urine production is influenced by renal blood flow (dictated by placental blood flow) and hormonal influence (vasopressin, aldosterone)
Amniotic fluid production from fetal lung
produce fluid to expand lungs to facilitate growth
200ml/day
excess fluid leaves lungs during breathing movements - 50% swallowed, 50% into AF
clinical implications for testing fetal lung maturity via amniocentesis (surfactant testing)
Fetal swallowing of AF
main route of fluid resorption
starts in 2nd trimester
500-1000 ml/day
Intramembranous flow of amniotic fluid
flow from fetal compartment to fetal compartment
hypotonic AF resorbed across osmotic gradient to vascular fetal surface of placenta
200-400 ml/day
Amniotic fluid production at term
Fetal urine 800-1200 ml
lung liquid 200 ml
Amniotic fluid resorption at term
fetal swallowing 500-1000 ml
intramembranous pathway 200-400 ml
Assessing amniotic fluid volume
ultrasound
AFI (amniotic fluid index): sum of deepest vertical pocket in 4 quadrants in mm (normal 50-250 )
DVP (Deepest vertical pocket) normal 20-80 mm
Objective measure and subjective assessment have both been proven to be reliable
Clinical assessment by SFH may raise suspicion of abnormal AFV
Oligohydramnios
AFI
Oligohydramnios chronic causes
Fetal anomalies: renal agenesis multicystic dysplastic kidneys Bilateral UPJ obstruction posterior urethral valves
Chronic fetal hypoxia
Growth restriction (uteroplacental insufficiency)
post-term pregnancy
chronic maternal hypoxia
maternal NSAID use
maternal dehydration
Complications due to oligohydramnios
limb contractures facial deformities pulmonary hypoplasia umbilical cord compression prematurity (iatrogenic) death
Oligohydramnios treatment
generally we cannot treat/modify long-term complications
Only successful when we can treat underlying cause (bladder shunts for bladder outlet obstruction)
Others have been tried:
- maternal hydration - only useful if dehydrated
- serial amnioinfusion: limited success, significant risks
- Amnio plugging for ruptured membranes - no benefit
Polyhydramnios
AFI > 250 mm or DVP > 8 cm
excess accumulation of amniotic fluid
Fetal etiology of polyhydramnios
structural: decreased swallowing due to GI obstruction, neurological impairment Cardiac arrhythmias infections genetic syndromes hematologic hydrops
Maternal etiology of polyhydramnios
isoimmunization (hydrops)
diabetes - ?glucose load
Placental etiology of polyhydramnios
chorioangioma
twin-to-twin tarnsfusion syndrome
Complications of polyhydramnios
Premature/preterm rupture of membranes preterm labour maternal discomfort fetal malpresentation in labour umbilical cord prolapse antepartum and postpartum hemorrhage
Treatment of polyhydramnios
Serial amniotic fluid dcompression via amniocentesis (up to 3L each time)
NSAIDs: historical - rarely used now; knock out fetal kidneys
Treat underlying condition
- laser for TTTS
- intrauterine fetal transfusion for anemia
- fetal surgery for resection of lung mass
Maternal oxygen capacity
total oxygen content in arterial blood
influenced by:
- Hb concentration/saturation (almost completely saturated)
- Hb oxygen affinity (Temp, acidity, 2,3-DPG levels)
- dissolved oxygen
Optimal maternal oxygenation requires adequate ventilation/pulmonary integrity
Uterine blood flow
Not autoregulated - dependent on maternal BP
Can impact fetal oxygenation
- hypertensive disease with v/c
- hypotension - supine hypotensive syndrome, severe hemorrhage
During labour: contractions reduce blood flow - many short contractions rather than a long one
Oxygen transfer at placenta
not all of O2 from intervillous space gets to fetus
- shunting: diverted to placenta/uterus (10-30% for placenta)
- uneven placental perfusion
- diffusing capacity of placenta for oxygen
Oxygen transfers from mother–> fetus because:
- O2 gradient
Bohr effect
fetal Hb has higher affinity for O2 than maternal Hb (curve shifted to left)
Mean pO2 of mother’s blood
arterial - 100 mmHg
intervillous space - 50 mmHg
Mean pO2 of fetus
umbilical vein: 30 mmHg
umbilical artery: 20
Bohr effect in placenta
Intervillous space:
Fetal metabolites/CO2 pass to mother
- IVS becomes more acidic –> facilitates O2 release from mother as maternal curve shifts right
As fetus gives up CO2, fetal pH rises –> shifts curve further left –> facilitates O2 uptake
CO2 exchange at placenta
from fetus to mother
CO2 gradient exists due to physiological hyperventilation of pregnancy
Mean pCO2 of fetus/mother
umbilical artery: 48 mmHg
intervillous space: 43
maternal blood: 30
maternal blood has higher affinity for CO2
fetal oxygen capacity
influenced by:
-fetal Hb concentration/oxygen affinity
Low absolute pO2 but can perfuse efficiently due to:
- higher Hb concentration, higher O2 capacity (HbF), higher CO
Physiologically, low pO2 helpful because it keeps DA open and pulmonary vascular bed constricted
Fetal Hemoglobin
more concentrated/ different structure
Different globin chains
Fetal acid-base exchange
Fetus produces carbonic acids and organic acids (lactate, ketones)
Carbonic acid
produced by fetus during normal oxidative metabolism
dissociates into CO2 and H2O
CO2 rapidly diffuses across placenta
Organic acids
result from anaerobic metabolism, e.g. lactic acid
Produced when fetal oxygenation impaired
- reduced placental oxygen transfer
- umbilical cord collapse
Organic acids cross placenta slowly (hours instead of seconds)
- lactic acids require specific, pH-dependent carrier
Placental acid-base exchange problems
if blood flow interrupted for a brief time period (e.g. placental abruption, cord compression)
–> fetal pH drops and CO2 rises –> respiratory acidosis
If oxygen lack is sustained,
- fetus decreases O2 consumption
- redistributes blood flow to vitals
- relies partly on anaerobic metabolism to meet energy needs –> anaerobic metabolism
Fetus copes with excess organic acids by buffering: Hb and bicarbonate
- if too much lactate, can be overwhelmed –> metabolic acidosis
Umbilical cord gases
drawn at every high risk delivery to determine acid-base status of fetus to reflect metabolic/respiratory demand
1) look at pH: pathologic increased risk of brain injury, seizures, need to CPR/NICU admin
then:
2) pCO2 - respiratory acidosis? HCO3- and BE: metabolic acidosis?
Base excess of fetus
HCO3- excess
buffers depleted in attempt to normalize pH as fetal acidemia worsens
“base” value –> amount of organic acids produced by fetus
larger base excess = worse severity/duration of anaerobic metabolism or impaired fetal oxygenation
Prefer to look at umbilical artery values
Respiratory acidosis in fetus
pH 60 high
HCO3- normal (short duration of respiratory acidosis; buffer not depleted yet)
BE normal
Metabolic acidosis in fetus
fetal oxygenation impaired for sustained time period
buffer used up - subsequent anaerobic metabolism
pH
