Pediatric Respiratory Physiology
Drs. Greg and Joy Loy Gordon
February 2005
Pediatric Respiratory Physiology
Prenatal – Embryo
Ventral pouch in primitive foregut becomes
lung buds projecting into pleuroperitoneal cavity
Endodermal part develops into
airway
alveolar membranes
glands
Mesenchymal elements develop into
smooth muscle
cartilage
connective tissue
vessels
Pediatric Respiratory Physiology
Prenatal Development
Pseudoglandular period – starting 17th week of gestation
Branching of airways down to terminal bronchioles
Canalicular period
Branching in to future respiratory bronchioles
Increased secretary gland and capillary formation
Terminal sac (alveolar) period
24th week of gestation
Clusters of terminal air sacs with flattened epithelia
Pediatric Respiratory Physiology
Surfactant
Produced by type II pneumocytes
appear 24-26 weeks (as early as 20 weeks)
Maternal glucocorticoid treatment 24-48 hours before delivery
accelerates lung maturation and
surfactant production
Premature birth – immature lungs ->
IRDS (HMD) due to insufficient surfactant production
Pediatric Respiratory Physiology
Prenatal Development
Proliferation of capillaries around saccules sufficient for gas exchange
26-28th week (as early as 24th week)
Formation of alveoli
32-36 weeks
saccules still predominate at birth
Pediatric Respiratory Physiology
Prenatal Development
Lung Fluid
expands airways -> helps stimulate lung growth
contributes ⅓ of total amniotic fluid
prenatal ligation of trachea in congenital diaphragmatic hernia
results in accelerated growth of otherwise hypoplastic lung
(J Pediatr Surg 28:1411, 1993)
Pediatric Respiratory Physiology
Perinatal adaptation
First breath(s)
up to 40 (to 80 cmH2O needed
to overcome high surface forces
to introduce air into liquid-filled lungs
adequate surfactant essential for smooth transition
Elevated PaO2
Markedly increased pulmonary blood flow ->
increased left atrial pressure with
closure of foramen ovale
Pediatric Respiratory Physiology
Postnatal development
Lung development continues for 10 years
most rapidly during first year
At birth: 20-50x107 terminal air sacs (mostly saccules)
only one tenth of adult number
Development of alveoli from saccules
essentially complete by 18 months of age
Pediatric Respiratory Physiology
Infant lung volume disproportionately small in relation to body size
VO2/kg = 2 x adult value
=> ventilatory requirement per unit lung volume is increased
less reserve
more rapid drop in SpO2 with hypoventilation
Pediatric Respiratory Physiology
Neonate
Lung compliance high
elastic fiber development occurs postnatally
static elastic recoil pressure is low
Chest wall compliance is high
cartilaginous ribs
limited thoracic muscle mass
More prone to atalectasis and respiratory insufficiency
especially under general anesthesia
Infancy and childhood
static recoil pressure steadily increases
compliance, normalized for size, decreases
Pediatric Respiratory Physiology
Infant and toddler
more prone to severe obstruction of upper and lower airways
absolute airway diameter much smaller that adult
relatively mild inflammation, edema, secretions
lead to greater degrees of obstruction
Pediatric Respiratory Physiology
Control of breathing – prenatal development
fetal breathing
during REM sleep
depressed by hypoxia
(severe hypoxia -> gasping)
may enhance lung growth and development
Pediatric Respiratory Physiology
Control of breathing – perinatal adaptation
Neonatal breathing is a continuation of fetal breathing
Clamping umbilical cord is important stimulus to rhythmic breathing
Relative hyperoxia of air augments and maintains rhythmicity
Independent of PaCO2; unaffected by carotid denervation
Hypoxia depresses or abolishes coninuous breathing
Pediatric Respiratory Physiology
Control of breathing – infants
Ventilatory response to hypoxemia
first weeks (neonates)
transient increase -> sustained decrease
(cold abolishes the transient increase in 32-37 week premaures
by 3 weeks
sustained increase
Ventilatory response to CO2
slope of CO2-response curve
decreases in prematures
increases with postnatal age
neonates: hypoxia
shifts CO2-response curve and
decreases slope
(opposite to adult response)
Pediatric Respiratory Physiology
Periodic breathing
apneic spells < 10 seconds
without cyanosis or bradycardia
(mostly during quiet sleep)
80% of term neonates
100% of preterms
30% of infants 10-12 months of age
may be abolished by adding 3% CO2 to inspired gas
Pediatric Respiratory Physiology
Central apnea
apnea > 15 seconds or
briefer but associated with
bradycardia (HR<100)
cyanosis or
pallor
rare in full term
majority of prematures
Pediatric Respiratory Physiology
Postop apnea in preterms
Preterms < 44 weeks postconceptional age (PCA): risk of apnea = 20-40%
most within 12 hours postop (Liu, 1983)
Postop apnea reported in reported in prematures as old as 56 weeks PCA
(Kurth, 1987)
Associated factors
extent of surgery
anesthesia technique
anemia
postop hypoxia
(Wellborn, 1991)
44-60 weeks PCA: risk of postop apnea < 5% (Cote, 1995)
Except: Hct < 30: risk remains HIGH independent of PCA
Role for caffeine (10 mg/kg IV) in prevention of postop apnea in prematures?
(Wellborn, 1988)
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Upper airway
Pharyngeal receptors ->
inhibition of breathing
closure of larynx
contraction of pharyngeal swallowing muscles
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Upper airway - Larynx
three receptor types
pressure
drive (irritant)
flow (or cold)
response to stimulus
apnea
coughing
closure of glottis
laryngospasm
changes in ventilatory pattern
newborn
increased sensitivity to superior laryngeal nerve stimulus ->
ventilatory depression or apnea
H2O more potent stimulus than normal saline ([Cl-])
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Infant (especially preterm) reflex response to fluid at entrance to larynx
Normal protective
swallowing
central apnea (H2O > NS)
sneezing
laryngeal closure
coughing or awakening (less frequent)
During inhalation induction
pharyngeal swallowing reflex abolished
laryngeal reflex intact ->
breath holding or central apnea
positive pressure ventilation may ->
push secretions into larynx ->
laryngospasm
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Laryngospasm
Sustained tight closure of vocal cords
by contraction of adductor (cricothyroid) muscles
persisting after removal of initial stimulus
More likely (decreased threshold) with
light anesthesia
hyperventilation with hypocapnia
Less likely (increased threshold) with
hypoventilation with hypercapnia
positive intrathoracic pressure
deep anesthesia
maybe positive upper airway pressure
Hypoxia (paO2 < 50) increases threshold (fail-safe mechanism?)
So:
suction before extubation while
patient relatively deep and
inflate lungs and maybe a bit of PEEP at time of extubation
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Slowly adapting (pulmonary stretch) receptors (SARs)
Posterior wall of trachea and major bronchi
Stimulus
distension of airway during inspiration
hypocapnia
Response
inhibit inspiratory activity
(Hering-Breuer inflation reflex)
May be related to adult apnea with ETT cuff inflated
during emergence from anesthesia and
rhythmic breathing promptly on cuff deflation
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
Rapidly adapting (irritant) receptors (RARs)
Especially carina and large bronchi
Stimulus
lung distortion
smoke
inhaled anesthetics
histamine
Response
coughing
bronchospasm
tracheal mucus secretion
Likely mediate the paradoxical reflex of Head:
with vagal afferents partially blocked by cold,
inflation of lungs ->
sustained contraction of diaphragm with
prolonged inflation
may be related to
sigh mechanism (triggered by collapse of parts of lung
during quiet breathing and increasing surface force)
neonatal response to mechanical lung inflation with
deep gasping breath
Pediatric Respiratory Physiology – Pulmonary and Thoracic Receptors
C-fiber endings (J-receptors)
Juxta-pulmonary receptors
Stimulus
pulmonary congestion
edema
micro-emboli
inhaled anesthetic agents
Response
apnea followed by
rapid, shallow breathing
bronchospasm
hypersecretion
hypotension
bradycardia
maybe laryngospasm
Pediatric Respiratory Physiology – Chemical Control of Breathing
Central Chemoreceptors
Near surface of ventrolateral medulla
Stimulus
[H+]
(pH of CSF and interstitial fluid;
readily altered by changes in paCO2)
Response
increased ventilation, hyperventilation
Pediatric Respiratory Physiology – Chemical Control of Breathing
Peripheral Chemoreceptors
Carotid bodies
3 types of neural components
type I (glomus) cells
type II (sheath) cells
sensory nerve fiber endings
carotid nerve ->
C.N. IX, glossopharyngeal nerve
Stimulus
paCO2 and pH
paO2 (especially < 60 mmHg)
Response – increased ventilation
Contribute 15% of resting ventilatory drive
Neonate: hypoxia depresses ventilation
by direct suppression of medullary centers
Pediatric Respiratory Physiology – Chemical Control of Breathing
Pediatric Respiratory Physiology – Chemical Control of Breathing
Chronic hypoxemia (for years)
Carotid bodies lose hypoxemic response
E.g., cyanotic congenital heart disease
(but hypoxic response does return after correction
and restoration of normoxia)
Pediatric Respiratory Physiology – Chemical Control of Breathing
Chronic respiratory insufficiency with hypercarbia
Hypoxemic stimulus of carotid chemoreceptors
becomes primary stimulus of respiratory centers
Administration of oxygen may ->
hypoventilation with
markedly elevated paCO2
Pediatric Respiratory Physiology – Assessment of Respiratory Control
CO2 response curve
Pediatric Respiratory Physiology – Assessment of Respiratory Control
Effects of anesthesia on respiratory control
Shift CO2 response curve to right
Depress genioglossus, geniohyoid, other phayrngeal dilator muscles ->
upper airway obstruction (infants > adults)
work of breathing decreased with
jaw lift
CPAP 5 cmH2O
oropharyngeal airway
LMA
Active expiration (halothane)
Pediatric Respiratory Physiology – Lung Volumes and Mechanics of Breathing
= 60 ml/kg infant
after 18 months
increases to
adult 90 ml/kg
by age 5
= 50% of TLC
may be only 15% of TLC in
young infants under GA
plus muscle relaxants
= 25% TLC
Pediatric Respiratory Physiology – Lung Volumes and Mechanics of Breathing
Elastic properties, compliance and FRC
Neonate chest wall compliance, CW = 3-6 x CL, lung compliance
tending to decrease FRC, functional residual capacity
By 9-12 months CW = CL
Dynamic FRC in awake, spontaneously ventilating infants is maintained
near values seen in older children and adults because of
1. continued diaphragmatic activity in early expiratory phase
2. intrinsic PEEP (relative tachypnea with start of inspiration
before end of preceding expiration)
3. *sustained tonic activity of inspiratory muscles
(probably most important)
By 1 year of age, relaxed end-expiratory volume predominates
Pediatric Respiratory Physiology – Lung Volumes and Mechanics of Breathing
Under general anesthesia, FRC declines by
10-25% in healthy adults with or without muscle relaxants and
35-45% in 6 to 18 year-olds
In young infants under general anesthesia
especially with muscle relaxants
FRC may = only 0.1 - 0.15 TLC
FRC may be < closing capacity leading to
small airway closure
atalectasis
V/Q mismatch
declining SpO2
Pediatric Respiratory Physiology – Lung Volumes and Mechanics of Breathing
General anesthesia, FRC and PEEP
Mean PEEP to resore FRC to normal
infants < 6 months 6 cm H2O
children
6-12 cm H2O
PEEP
important in children < 3 years
essential in infants < 9 months
under GA + muscle relaxants
(increases total compliance by 75%)
(Motoyama)
Pediatric Respiratory Physiology – Dynamic Properties
Poiseuille’s law for laminar flow:
where
R = 8lη/πr4
For turbulent flow:
R resistance
l length
η viscosity
R α 1/r5
Upper airway resistance
adults: nasal passages: 65% of total resistance
Infants: nasal resistance 30-50% of total
upper airway: ⅔ of total resistance
NG tube increases total resistance up to 50%
Pediatric Respiratory Physiology
Anesthetic effects on respiratory mechanics
Relaxation of respiratory muscles ->
decreased FRC
cephalad displacement of diaphragm
contributes to decreased FRC
much less if patient not paralyzed
airway closure
atalectasis
minimized by PEEP 5 cm H2O in children
process slowed by 30-40% O2 in N2 (vs 100% O2)
V/Q mismatch
Endotracheal tube adds the most significant resistance
Pediatric Respiratory Physiology
Ventilation and pulmonary circulation
Infants: VA per unit of lung volume > adult because of
relatively higher metabolic rate, VO2
relatively smaller lung volume
Infants and toddlers to age 2 years:
VT preferentially distributed to uppermost part of lung
Pediatric Respiratory Physiology
Oxygen transport
(Bohr effect)
= 27, normal adult (19, fetus/newborn)
Pediatric Respiratory Physiology
Oxygen transport
Bohr effect
increasing pH (alkalosis) decreases P50
beware hyperventilation decreases tissue oxygen delivery
Hgb F
reacts poorly with 2.3-DPG
P50 = 19
By age
3 months
9 months
P50 = 27 (adult level)
P50 peaks at 29-30
Pediatric Respiratory Physiology
Oxygen transport
If SpO2 = 91
then = PaO2 =
Adult
6 months
6 weeks
6 hours
60
66
55
41
Pediatric Respiratory Physiology
P50
Oxygen transport
Hgb for equivalent tissue oxygen delivery
Adult
27
8
10
12
> 3 months
30
6.5
8.2
9.8
< 2 months
24
11.7
14.7
17.6
Implications for blood transfusion
older infants may tolerate somewhat lower Hgb levels at which
neonates ought certainly be transfused
Pediatric Respiratory Physiology
Surfactant
Essential phospholipid protein complex
Regulates surface tension
Stabilizing alveolar pressure
LaPlace equation
P = nT/r
where P ressure
r adius of small sphere
T ension
n = 2 for alveolus
Surface tension: 65% of elastic recoil pressure
Pediatric Respiratory Physiology
Surfactant
Produced by cuboidal type II alveolar pneumocytes (27th week)
Lecithin (phosphatidylcholine, PC)/sphingomyelin (L/S) ratio
in amniotic fluid correlates with lung maturity
Pediatric Respiratory Physiology
Surfactant
Synthesis increased by
glucocorticoids
thyroxine
heroin
cyclic adenosine monophosphate (cAMP)
epidermal growth factor
tumor necrosis factor alpha
transforming growth factor beta
Synthetic surfactant used in treatment of
premature infants with surfactant deficiency
PPHN
CDH
meconium aspiration syndrome
ARDS (adults and children)
Pediatric Respiratory Physiology – Selected Points
Basic postnatal adaptation lasts until 44 weeks postconception,
especially in terms of respiratory control
Postanesthetic apnea is likely in prematures, especially anemic
Formation of alveoli essentially complete by 18 months
Lung elastic and collagen fiber development continues through age 10 years
Young infant chest wall is very compliant and
incapable of sustaining FRC against lung elastic recoil when
under general anesthesia, especially with muscle relaxants
leading to airway closure and
‘progressive atalectasis of anesthesia’
Mild – moderate PEEP (5 cmH2O) alleviates
Hemoglobin oxygen affinity changes dramatically first months of life
Hgb F – low P50 (19)
P50 increases, peaks in later infancy (30)
implications for blood transfusion