Pulmonary Physiology

AnS 536

Spring 2015

Pulmonary Development in the Fetus

Fetal lung development Accelerated through in utero treatment with

corticosteroids and thyroid hormones Factors enhancing pulmonary phospholipid

metabolism Catecholamines Thyrotropin-releasing hormone Estradiol Heroin Cyclic AMP

Pulmonary Development in the Fetus

Glucocorticoids Contribute to the development of lung morphology and the

surfactant system in type II cells More stable lungs Increased air space

Glucocorticoid action 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 Corticosteroid therapy

Used during premature labor Reduces incidence of respiratory distress

syndrome Endogenous cortisol sources:

Fetal adrenal glands Maternal adrenal glands Conversion of cortisone to cortisol by amniotic

membranes and lung fibroblasts

Pulmonary Development in the Fetus Thyroid hormones

Effects similar to corticosteroids 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 Inspired gas composition Barometric pressure Temperature Respiratory quotient Replenishment with fresh gas Uptake of oxygen from alveoli into blood

Dependent on cardiac output and [Hb] 4 through 6 are primary determinants

Respiratory Quotient

R=CO2 entering alveoli/O2 entering blood Dependent on the metabolic substrate

consuming oxygen and producing carbon dioxide Glucose (R=1) Lipids (R=0.7) Mixed (R=0.825)

O2 Transport Across the Neonatal Lungs Primary determinant of oxygen flow rate into

a cell is the PO2 in the capillaries Second determinant is rate that the cell

consumes oxygen Function of mitochondrial density

Oxygen consumption of newborns is extremely high ~3-fold increase over fetal levels

Increase in oxygen consumption necessary primarily to maintain body temperature

O2 and CO2 Transport Across the Neonatal Lungs 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

HbF levels decrease with age

Surfactant Complex mixture of phospholipids (especially

dimalmitoyl lecithin) and proteins Synthesized and stored by type II alveolar epithelial

cells Has the ability to reduce surface tension at the

air-liquid interface Maintains alveolar expansion and expiration Increases pulmonary compliance

Reduces the work of inflating the lungs Reduces the lungs’ tendency to recoil

Do not collapse as readily

Surfactant

Vital to neonatal survival Essential in gas exchange

Allows exchange to occur at low trans-pulmonary pressures

Restores collapsed lung regions Results in marked increase in oxygen saturation

and perfusion Glucocorticoid treatment

Increases surfactant associated proteins and phospholipids increase surfactant production

Surfactant Factors mediating production

Early gestation Glucocorticoid

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 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 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 Assists in resorption of fluids and surfactant

becomes plastered on walls of lungs

Stimulus for First Breath

Stoppage of umbilical circulation Takes about a minute

Cold, especially in face and forehead regions Heat produces apnea

The First Breath

Involves both diaphragm and upper airway muscles

Pleural pressure peaks at 30-100 cm H2O Normal pleural pressure is 5-7 cm H2O

Tidal volume is 35-45 ml Double the normal VT

Distribution of air is uneven First expiration slow and long

After the First Breath Respiratory pattern following the first breath

Slow and irregular pattern 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

Newborns are obligate nose breathers Occlusion of nasal passages can theoretically

result in suffocation Can initially inhale through mouth only by

extending the spine and opening mouth wide to retract epiglottis Oral suction does more harm than good

Can switch to mouth breathing eventually, but switch takes longer than in adults

Evaluating Lung Function Fetus

Measured through the L/S ratio test Measures lecithin and sphingomyelin concentrations in the

amniotic fluid Helps determine maturity of fetal lungs prior to birth

Neonates Pulse oximetry Pulmonary Function Tests (PFT)

Measures lung function in ill neonates Tests include:

Tidal volume Minute ventilation Respiratory rate Pulmonary compliance Resistance Resistive work of breathing Functional residual capacity

Amniocentesis

http://www.youtube.com/watch?v=DjAXK4rY9qs&feature=player_detailpage

Respiratory Distress Syndrome (RDS) 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) Treatments

Initially high O2 and humidity concentrations are given

Severe cases may use ventilator to maintain adequate O2 concentrations and pressure levels

Exogenous surfactant therapy Given to infants prior to 30 weeks of age

Preterm administration of corticosteroids Dexamethasone and/or betamethasone Lungs rich in glucocorticoid receptors