pediatric respiratory physiology drs. greg and joy loy gordon february 2005

Pediatric Respiratory Physiology

Drs. Greg and Joy Loy GordonFebruary 2005


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


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

Prenatal Development


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


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



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)



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


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


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


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


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


Control of breathing – prenatal development

fetal breathing

during REM sleep

depressed by hypoxia

(severe hypoxia -> gasping)

may enhance lung growth and development


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


Control of breathing – infantsVentilatory response to hypoxemia

first weeks (neonates)transient increase -> sustained decrease(cold abolishes the transient increase in 32-37 week premaures

by 3 weekssustained 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)


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


Central apnea

apnea > 15 seconds or

briefer but associated with

bradycardia (HR<100)

cyanosis or

pallor

rare in full term

majority of prematures


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 factorsextent of surgeryanesthesia techniqueanemiapostop 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


Upper airway - Larynx

three receptor typespressuredrive (irritant)flow (or cold)

response to stimulusapneacoughingclosure of glottislaryngospasmchanges in ventilatory pattern

newbornincreased sensitivity to superior laryngeal nerve stimulus ->

ventilatory depression or apneaH2O more potent stimulus than normal saline ([Cl-])


Infant (especially preterm) reflex response to fluid at entrance to larynx

Normal protectiveswallowingcentral apnea (H2O > NS)sneezinglaryngeal closurecoughing or awakening (less frequent)

During inhalation inductionpharyngeal swallowing reflex abolishedlaryngeal reflex intact ->

breath holding or central apneapositive pressure ventilation may ->

push secretions into larynx ->laryngospasm


Laryngospasm

Sustained tight closure of vocal cords by contraction of adductor (cricothyroid) musclespersisting after removal of initial stimulus

More likely (decreased threshold) withlight anesthesiahyperventilation with hypocapnia

Less likely (increased threshold) withhypoventilation with hypercapniapositive intrathoracic pressuredeep anesthesiamaybe 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


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


Rapidly adapting (irritant) receptors (RARs)

Especially carina and large bronchiStimulus

lung distortionsmokeinhaled anestheticshistamine

Responsecoughingbronchospasmtracheal mucus secretion

Likely mediate the paradoxical reflex of Head:with vagal afferents partially blocked by cold,inflation of lungs ->

sustained contraction of diaphragm withprolonged 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


C-fiber endings (J-receptors)

Juxta-pulmonary receptorsStimulus

pulmonary congestionedemamicro-emboliinhaled anesthetic agents

Responseapnea followed by rapid, shallow breathingbronchospasmhypersecretionhypotensionbradycardiamaybe 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


Peripheral Chemoreceptors

Carotid bodies3 types of neural components

type I (glomus) cellstype II (sheath) cellssensory nerve fiber endings

carotid nerve ->C.N. IX, glossopharyngeal nerve

StimuluspaCO2 and pHpaO2 (especially < 60 mmHg)

Response – increased ventilationContribute 15% of resting ventilatory driveNeonate: hypoxia depresses ventilation

by direct suppression of medullary centers


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)


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

50% of TLC =

= 25% TLC

= 60 ml/kg infant

after 18 monthsincreases to adult 90 ml/kgby age 5

may be only 15% of TLC in young infants under GAplus muscle relaxants


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 maintainednear values seen in older children and adults because of

1. continued diaphragmatic activity in early expiratory phase2. 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


Under general anesthesia, FRC declines by

10-25% in healthy adults with or without muscle relaxants and35-45% 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


General anesthesia, FRC and PEEP

Mean PEEP to resore FRC to normalinfants < 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:

R = 8lη/πr4where R resistance

l lengthη viscosity

For turbulent flow: 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%


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


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)


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 P50 = 27 (adult level)

9 months P50 peaks at 29-30


If SpO2 = 91

then = PaO2 =

Adult 606 months 666 weeks 556 hours 41


Implications for blood transfusion

older infants may tolerate somewhat lower Hgb levels at which

neonates ought certainly be transfused

P50 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


Surfactant

Essential phospholipid protein complexRegulates surface tensionStabilizing alveolar pressure

LaPlace equationP = nT/rwhere P ressure

r adius of small sphereT ensionn = 2 for alveolus

Surface tension: 65% of elastic recoil pressure

Pediatric Respiratory PhysiologySurfactant

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 PhysiologySurfactant

Synthesis increased byglucocorticoidsthyroxineheroincyclic adenosine monophosphate (cAMP)epidermal growth factortumor necrosis factor alphatransforming growth factor beta

Synthetic surfactant used in treatment ofpremature infants with surfactant deficiency PPHNCDHmeconium aspiration syndromeARDS (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

pediatric respiratory physiology drs. greg and joy loy gordon february 2005

Documents

respiratory insufficiency

hypoventilation slide

lung growth

future respiratory bronchioles

lung maturation

months of age slide

unit lung volume

lung buds projecting