Pulmonary Physiology
AnS 536
Spring 2015
Pulmonary Development in the Fetus
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Fetal lung development
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Accelerated through in utero treatment with
corticosteroids and thyroid hormones
Factors enhancing pulmonary phospholipid
metabolism
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Catecholamines
Thyrotropin-releasing hormone
Estradiol
Heroin
Cyclic AMP
Pulmonary Development in the Fetus
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Glucocorticoids
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Contribute to the development of lung morphology and the
surfactant system in type II cells
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More stable lungs
Increased air space
Glucocorticoid action
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Induction of an enzyme
Mediated by interaction of steroid with cytoplasmic glucocorticoid
receptors
Receptors present in the lung, pulmonary fibroblasts, and type II
cells
Pulmonary Development in the Fetus
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Corticosteroid therapy
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Used during premature labor
Reduces incidence of respiratory distress
syndrome
Endogenous cortisol sources:
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Fetal adrenal glands
Maternal adrenal glands
Conversion of cortisone to cortisol by amniotic
membranes and lung fibroblasts
Pulmonary Development in the Fetus
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Thyroid hormones
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Effects similar to corticosteroids
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Different biochemical steps
Synthetic analogues of triiodothyronine (T3)
readily cross the placenta and accelerate
surfactant synthesis and release
Act through nuclear receptors present in the lung
Thyroid treatment in utero appears to accelerate
lung maturation and prevent respiratory distress
syndrome in premature infants
Determinants of Alveolar Gas Composition
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Inspired gas composition
Barometric pressure
Temperature
Respiratory quotient
Replenishment with fresh gas
Uptake of oxygen from alveoli into blood
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Dependent on cardiac output and [Hb]
4 through 6 are primary determinants
Respiratory Quotient
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R=CO2 entering alveoli/O2 entering blood
Dependent on the metabolic substrate
consuming oxygen and producing carbon
dioxide
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Glucose (R=1)
Lipids (R=0.7)
Mixed (R=0.825)
O2 Transport Across the Neonatal Lungs
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Primary determinant of oxygen flow rate into
a cell is the PO2 in the capillaries
Second determinant is rate that the cell
consumes oxygen
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Oxygen consumption of newborns is
extremely high
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Function of mitochondrial density
~3-fold increase over fetal levels
Increase in oxygen consumption necessary
primarily to maintain body temperature
O2 and CO2 Transport Across the
Neonatal Lungs
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Initial breath of the neonate promotes closure
of the ductus arteriosus and increases blood
flow into the lungs
O2 exchanged in alveoli to capillaries
CO2 generated from metabolism of CHO’s is
unloaded in the alveoli
Fetal Hb important in binding O2
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HbF levels decrease with age
Surfactant
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Complex mixture of phospholipids (especially
dimalmitoyl lecithin) and proteins
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Synthesized and stored by type II alveolar epithelial
cells
Has the ability to reduce surface tension at the
air-liquid interface
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Maintains alveolar expansion and expiration
Increases pulmonary compliance
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Reduces the work of inflating the lungs
Reduces the lungs’ tendency to recoil
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Do not collapse as readily
Surfactant
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Vital to neonatal survival
Essential in gas exchange
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Restores collapsed lung regions
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Allows exchange to occur at low
trans-pulmonary pressures
Results in marked increase in oxygen saturation
and perfusion
Glucocorticoid treatment
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Increases surfactant associated proteins and
phospholipids  increase surfactant production
Surfactant
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Factors mediating production
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Early gestation
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Glucocorticoid
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Receptor is expressed in the fetal lung
Stimulate the production of surfactant-associated proteins
Increases phospholipid synthesis by enhancing activity of
phosphatidylcholine (main component of surfactant)
Late gestation
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Surfactant production has been found at week 23 of
gestation
Infants born before this time frame have difficulty surviving
due to depressed surfactant levels
Surfactant
http://www.youtube.com/watch?v=tLpUTL1
-QEw&feature=player_detailpage
Normal Birth and the First Breath
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Compression of thorax in birth canal
eliminates much fluid and mucus especially in
upper portions of respiratory tract
Thoracic recoil as fetus leaves birth canal
helps produce “pull” on lungs (along with
expansion by means of respiratory muscles)
and dilates lymph and blood vessels
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Assists in resorption of fluids and surfactant
becomes plastered on walls of lungs
Stimulus for First Breath
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Stoppage of umbilical circulation
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Takes about a minute
Cold, especially in face and forehead regions
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Heat produces apnea
The First Breath
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Involves both diaphragm and upper airway
muscles
Pleural pressure peaks at 30-100 cm H2O
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Tidal volume is 35-45 ml
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Normal pleural pressure is 5-7 cm H2O
Double the normal VT
Distribution of air is uneven
First expiration slow and long
After the First Breath
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Respiratory pattern following the first breath
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Slow and irregular pattern
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Frequent interruptions in expiration (occluded breaths)
Causes gas trapping
Helps distribute lung volume evenly
Helps clear fluids
Respiratory function develops through rapidly
increasing the lung volume
Resting volume stays small (high FRC)
Respiratory rate gradually increases
Premature infants have difficulty in adequate gas
exchange due to their underdeveloped lungs
Neonatal Breathing Issues
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Newborns are obligate nose breathers
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Can initially inhale through mouth only by
extending the spine and opening mouth wide
to retract epiglottis
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Occlusion of nasal passages can theoretically
result in suffocation
Oral suction does more harm than good
Can switch to mouth breathing eventually, but
switch takes longer than in adults
Evaluating Lung Function
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Fetus
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Measured through the L/S ratio test
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Measures lecithin and sphingomyelin concentrations in the
amniotic fluid
Helps determine maturity of fetal lungs prior to birth
Neonates
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Pulse oximetry
Pulmonary Function Tests (PFT)
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Measures lung function in ill neonates
Tests include:
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Tidal volume
Minute ventilation
Respiratory rate
Pulmonary compliance
Resistance
Resistive work of breathing
Functional residual capacity
Amniocentesis
http://www.youtube.com/watch?v=DjAXK4r
Y9qs&feature=player_detailpage
Respiratory Distress Syndrome (RDS)
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Occurs in neonates with underdeveloped
lungs
#1 complication in premature neonates
Affects 50% of babies born before
32 weeks
Significant cause of death and morbidity in
preterm infants
Inability to exchange O2 and CO2 adequately
due to underdeveloped or collapsed lungs
Respiratory Distress Syndrome (RDS)
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Treatments
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Initially high O2 and humidity concentrations are
given
Severe cases may use ventilator to maintain
adequate O2 concentrations and pressure levels
Exogenous surfactant therapy
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Given to infants prior to 30 weeks of age
Preterm administration of corticosteroids
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Dexamethasone and/or betamethasone
Lungs rich in glucocorticoid receptors