Pediatric anatomy, physiology & pharmacology

Pediatric Anatomy, Physiology &
Pharmacology
848th FST

Introduction
Of primary importance to the pediatric anesthesia
provider is the realization that infants and children
are not simply a small adult. Their anesthetic
management depends upon the appreciation of the
physiologic, anatomic and pharmacologic
differences between the varying ages and the
variable rates of growth. Also of importance is a
general knowledge of the psychological
development of children to enable the anesthetist to
provide measures to reduce fear and apprehension
related to anesthesia and surgery.

Definitions
• Preterm or Premature Infant: < 37 weeks
• Term Infant: 38-42 weeks gestation
• Post Term Infant: > 42 weeks gestation
• Newborn: up to 24 hours old
• Neonate: 1-30 days old
• Infant: 1-14 months old
• Child: 14 months to puberty (~12-13 years)

Body Size
• The most obvious difference between children &
adults is size
• It makes a difference which factor is used for
comparison: a newborn weighing 3kg is
– 1/3 the size of an adult in length
– 1/9 the body surface area
– 1/21 the weight
• Body surface area (BSA) most closely parallels
variations in BMR & for this reason BSA is a
better criterion than age or weight for calculating
fluid & nutritional requirements

Fetal Development
• The circulatory system is the first to achieve a
functional state in early gestation
– The developing fetus outgrows its ability to obtain &
distribute nutrients and O2 by diffusion from the
placenta
• The functioning heart grows & develops at the
same time it is working to serve the growing fetus
– At 2 months gestation the development of the heart and
blood vessels is complete
– In comparison, the development of the lung begins later
& is not complete until the fetus is near term

Fetal Circulation
• Placenta
– Gas exchange
– Waste elimination
• Umbilical Venous Tension is 32-35mmHg
– Similar to maternal mixed venous blood
– Result:
• O2 saturation of ~65% in maternal blood, but ~80% in the fetal
umbilical vein (UV)
– Low affinity of fetal Hgb (HgF) for 2,3-DPG as
compared with adult Hgb (HgA)
– Low concentration of 2,3-DPG in fetal blood
• O2 & 2,3-DPG compete with Hgb for binding, the
reduced affinity of HgF for 2,3-DPG causes the
Hgb to bind to O2 tighter
– Higher fetal O2 saturation

Fetal Circulation
• P50 is 27mmHg for adult Hgb, but only 20mmHg
for fetal Hgb
– This causes a left shift in the O2 dissociation curve
• Because the bridge between arterial & tissue O2
tension crosses the steep part of the curve, HgF
readily unloads O2 to the tissue despite its
relatively low arterial saturation

Fetal Circulatory Flow
• Starts at the placenta with the umbilical vein
– Carries essential nutrients & O2 from the placenta to
the fetus (towards the fetal heart, but with O2 saturated
blood)
• The liver is the first major organ to receive blood
from the UV
– Essential substrates such as O2, glucose & amino acids
are present for protein synthesis
– 40-60% of the UV flow enters the hepatic
microcirculation where it mixes with blood draining
from the GI tract via the portal vein
• The remaining 40-60% bypasses the liver and
flows through the ductus venosus into the upper
IVC to the right atrium (RA)

• The fetal heart does not distribute O2 uniformly
– Essential organs receive blood that contains more
oxygen than nonessential organs
– This is accomplished by routing blood through
preferred pathways
• From the RA the blood is distributed in two
directions:
– 1. To the right ventricle (RV)
– 2. To the left atrium (LA)
• Approximately 1/3 of IVC flow deflects off the
crista dividens & passes through the foramen
ovale of the intraatrial septum to the LA

• Flow then enters the LV & ascending aorta
– This is where blood perfuses the coronary and cerebral
arteries
• The remaining 2/3 of the IVC flow joins the
desaterated SVC (returning from the upper body)
mixes in the RA and travels to the RV & main
pulmonary artery
• Blood then preferentially shunts from the right to
the left across the ductus arteriosus from the main
pulmonary artery to the descending aorta rather
than traversing the pulmonary vascular bed
– The ductus enters the descending aorta distal to the
innominate and left carotid artery
– It joins the small amount of LV blood that did not
perfuse the heart, brain or upper extremities

• The remaining blood (with the lowest sat of 55%)
perfuses the abdominal viscera
• The blood then returns to the placenta via the
paired umbilical arteries that arise from the
internal iliac arteries
– Carries unsaturated blood from the fetal heart
• The fetal heart is considered a “Parallel”
circulation with each chamber contributing
separately, but additively to the total ventricular
output
– Right side contributing 67%
– Left side contributing 33%
• The adult heart is considered “Serial”

Cardiac Malformations
• The parallel nature of the two ventricles
enables fetuses with certain types of cardiac
malformations to undergo normal fetal
growth & development until term because
systemic blood flow is adequate in utero
– Complete left to right heart obstruction does not
impede fetal aortic blood flow
– The foramen ovale & ductus arteriosus provide
alternate pathways to bypass obstruction

• Summary:
– Ductus Venosus shunts blood from the UV to
the IVC bypassing the liver
– Foramen Ovale shunts blood from the RA to
the LA
– Ductus Arteriosus shunts blood from the PA to
the descending aorta bypassing the lungs
– Fetal circulation is parallel
– Blood from the LV perfuses the heart & brain
with well oxygenated blood

Fetal Pulmonary Circulation
• Fetal Lungs
– Extract O2 from blood with its main purpose to
provide nutrients for lung growth
• Neonatal Lungs
– Supply O2 to the blood
• Fetal lung growth requires only 7% of
combined ventricular output

Fetal Pulmonary Circulation
• Fetal pulmonary vascular resistance (PVR) is high
& helps restrict the amount of pulmonary blood
flow
– If not for the low resistance ductus arteriosus (DA) &
adjoining peripheral vascular bed the RV would need to
pump against a higher pulmonary resistance than the
LV
– Instead, both ventricles face relatively low systemic
vascular resistance established by the low resistance /
high flow from the placenta

Transitional & Neonatal
Circulation
• There are 3 steps to understanding transitional
circulation
– 1. Foramen Ovale: ductus arteriosus & ductus venosus
close to establish a heart whose chambers pump in
series rather than parallel
• Closure is initially reversible in certain circumstances & the
pattern of blood flow may revert to fetal pathways
– 2. Anatomic & Physiologic: Changes in one part of the
circulation affect other parts
– 3. Decrease in PVR: The principal force causing a
change in the direction & path of blood flow in the
newborn

Circulation
• Changes that establish the newborn
circulation are an “orchestrated” series of
interrelated events
– As soon as the infant is separated from the low
resistance placenta & takes the initial breath
creating a negative pressure (40-60cm H2O),
expanding the lungs, a dramatic decrease in
PVR occurs
– Exposure of the vessels to alveolar O2
increases the pulmonary blood flow
dramatically & oxygenation improves

Circulation
– Hypoxia and/or acidosis can reverse this
causing severe pulmonary constriction
– The pulmonary vasculature of the newborn can
also respond to chemical mediators such as
• Acetylcholine
• Histamine
• Prostaglandins
– **All are vasodilators

Circulation
• Most of the decrease in PVR (80%) occurs in the
first 24 hours & the PAP usually falls below
systemic pressure in normal infants
• PVR & PAP continue to fall at a moderate rate
throughout the first 5-6 weeks of life then at a
more gradual rate over the next 2-3 years
• Babies delivered by C-section have a higher PVR
than those born vaginally & it may take them up to
3 hours after birth to decrease to the normal range

Circulation

Persistent Pulmonary
Hypertension (PPHN)
• In 1969 a syndrome of central cyanosis was
observed in neonates who had no:
– Parenchymal pulmonary disease
– Abnormal intracardiac relationships
– Structural heart disease
• The syndrome was called persistent fetal
circulation (PFC) & was identified by:
– Increased PVR
– Patent foramen ovale
– Patent ductus arteriosus

Hypertension (PPHN)
• A failure of the newborn’s circulation system to
change from normal intrauterine to extrauterine
patterns results in an abnormal shunting of blood
from right to left via persistent fetal pathways
• However, because the placenta is no longer in
continuity with the newborn’s cardiovascular
system
– The condition is not really persistence of the fetal
circulation
– Therefore, the syndrome is more accurately referred to
as persistent pulmonary hypertension of the newborn
(PPHN)

Hypertension (PPHN)

Hypertension (PPHN)
• Treatment
– Optimal oxygenation
– Hyperventilation
– Sedation
– Paralysis
– Extracorporeal membrane oxygenation
(ECMO)
• Reserved for severe & persistent cases only

Hypertension (PPHN)
• Implications for Anesthesia:
– Pathophysiologic mechanisms that trigger this
condition
• Hypercarbia
• Acidosis
– Arterial Blood Sampling
• Right radial artery or temporal arteries
– More meaningful since these areas reflect the values in the blood
reaching the brain & coronary arteries
• Left radial artery
– May be misleading because the left subclavian is very close to
the ductus
– Pulse Oximeter Probes
• Should be placed on right upper limb or head

Closure of the Ductus Arteriosus,
Foramen Ovale & Ductus
Venosus

Ductus Arteriosus
• Closure occurs in two stages
– Functional closure occurs 10-15 hours after
birth
• This is reversible in the presence of hypoxemia or
hypovolemia
– Permanent closure occurs in 2-3 weeks
• Fibrous connective tissue forms & permanently
seals the lumen
– This becomes the ligamentum arteriosum

Persistent Ductus Arteriosus
• Also referred to as Pathologic PDA
– Requires surgical closure & differs from the
normal ductus in tissue structure
– The PDA in the preterm infant is due to a weak
vasoconstrictor response to O2 and should be
considered a normal not pathologic response
• This PDA may still need surgical correction
• A left to right shunt through the ductus can flood the
lungs of the premature infant prolonging mechanical
ventilation, eventually leading to pulmonary edema
& right sided heart failure

• Anesthetic Considerations
– Excessive fluids may reopen a ductus or permit
excessive left to right shunting through an
already open ductus
– Intraoperative short falls
• Strict fluid management
• Attention to acid base balance
• Oxygenation
• Ventilation
– All are very important in premature infants to avoid
reopening the ductus & causing CHF

• A PDA may also be beneficial
– In cyanotic congenital heart malformations with right to
left & decreased pulmonary blood flow
• The PDA may be the major route by which the blood reaches
the pulmonary arteries to receive O2
• In this case closure of the DA causes severe cyanosis, tissue
hypoxia & acidemia
• To keep the ductus open prior to palliative or corrective
surgery of the heart malformation, PGE 1 (0.05-
0.1mcg/kg/min) can be administered IV
• To help close the ductus prior to surgical intervention to ligate
the PDA, Indomethacin (0.1-0.2mg/kg) can be administered
– This is an inhibitor of PGE synthesis

Foramen Ovale
• Increased pulmonary blood flow & left atrial
distention help to approximate the two margins of
the foramen ovale
– This is a flap like valve & eventually the opening seals
closed
– This hole also provides a potential right to left shunt
– Crying, coughing & valsalva maneuver increases PVR
which increases RA & RV pressure
– A right to left atrial & intrapulmonary shunt may
therefore readily occur in newborns & young infants

Foramen Ovale
• Probe Patency
– Is present in 50% of children < 5 years old & in more
than 25% of adults
– Therefore, the possibility of right to left atrial shunting
exists throughout life & there is a potential avenue for
air emboli to enter the systemic circulation
– A patent FO may be beneficial in certain heart
malformations where mixing of blood is essential for
oxygenation to occur such as in transposition of the
great vessels
– Patients who rely on the patency of the foramen require
a balloon atrial septoplasty during a cardiac cath or a
surgical atrial septectomy

Ductus Venosus
• This has no purpose after the fetus is
separated from the placenta at delivery

Cardiovascular Differences in the
Infant
• There are gross structural differences & changes
in the heart during infancy
– At birth the right & left ventricles are essentially the
same in size & wall thickness
– During the 1st month volume load & afterload of the
LV increases whereas there is minimal increase in
volume load & decrease in afterload on the RV
• By four weeks the LV weighs more than the RV
• This continues through infancy & early childhood until the LV
is twice as heavy as the RV as it is in the adult

Infant
• Cell structure is also different
– The myocardial tissues contain a large number
of nuclei & mitochondria with an extensive
endoplasmic reticulum to support cell growth &
protein synthesis during infancy
• The amount of cellular mass dedicated to contractile
protein in the neonate & infant is less than the adult
– 30% vs. 60%
• These differences in the organization, structure &
contractile mass are partly responsible for the
decreased functional capacity of the young heart

Infant
• Both ventricles are relatively noncompliant
& this has two implications for the
anesthesia provider
– 1. Reduced compliance with similar size & wall
thickness makes the interrelationship of the
ventricular function more intimate
• Failure of either ventricle with increased filling
pressure quickly causes a septal shift &
encroachment on stroke volume of the opposite
ventricle

Infant
– 2. Decreased compliance makes it less sensitive
to volume overload & their ability to change
stroke volume is nearly nonexistent
• CO is not rate dependent at low filling pressures but
small amounts of fluid rapidly change filling
pressures to the plateau of the Frank-Starling length
tension curve where stroke volume is fixed
– This changes the CO to strictly being rate dependent
– Additional small amounts of fluid can push the filling
pressure to the descending part of the curve & the
ventricles begin to fail
– The normal immature heart is sensitive to volume
overloading

Infant
• Functional capacity of the neonatal & infant
heart is reduced in proportion to age & as
age increases functional capacity increases
– The time over which growth & development
overcome these limitations is uncertain &
variable
– When adult levels of systemic artery pressure &
PVR are achieved by age of 3 or 4 years the
above limitations probably no longer apply

Autonomic Control of the Heart
• Sympathetic
innervation of the
heart is incomplete at
birth with decreased
cardiac catecholamine
stores & it has an
increased sensitivity to
exogenous
norepinephrine
– It does not mature until 4-6
months of age
• Parasympathetic
innervation has been
shown to be complete
at birth therefore we
see an increased
sensitivity to vagal
stimulation

• The imbalance between sympathetic &
parasympathetic tone predisposes the infant
to bradycardia
– Anything that activates the parasympathetic
nervous system such as anesthetic overdose,
hypoxia or administration of Anectine can lead
to bradycardia
– If bradycardia develops in neonates & infants
always check oxygenation first

• Atropine may inhibit vagal stimulation
– Is always given prior to, or at the same time,
that Anectine is given or anytime that vagal
stimulation will be present such as in an awake
intubation
• Dose of Atropine is 20mcg/kg where the minimum
dose for children is 0.1mg
– Anything less than 0.1mg can cause paradoxical
bradycardia which may occur secondary to a dose
dependent (low dose) central vagal stimulating effect of
the drug

Circulation
• The vasomotor reflex arcs are functional in
the newborn as they are in adults
– Baroreceptors of the carotid sinus lead to
parasympathetic stimulation & sympathetic
inhibition
– There are less catecholamine stores & a blunted
response to catecholamines
• Therefore neonates & infants can show vascular
volume depletion by hypotention without
tachycardia

Cardiovascular Parameters
• Parameters are much different for the infant than
for the adult
– Heart rate: higher
• Decreasing to adult levels at ~5 years old
– Cardiac output: higher
• Especially when calculated according to body weight & it
parallels O2 consumption
– Cardiac index: constant
• Because of the infants high ratio of surface area to body weight
– O2 consumption: depends heavily on temperature
• There is a 10-13% increase in O2 consumption for each degree
rise in core temperature

Circulation Variables in Infants

Respiratory System
• Neonatal adaptation of lung mechanics &
respiratory control
– Takes several weeks to complete
• Beyond this immediate period the lungs are not fully
mature for another few years
– Formation of adult type alveoli begins at 36
weeks postconception
• Represents only a fraction of the terminal air sacs
with thick septa
• It takes more than several years for functional and
morphologic development to be complete

Respiratory System
• Neural & chemical controls of breathing in older
infants & children are similar to those in
adolescents & adults
– A major exception to this is found in neonates and
young infants, especially in premature infants less than
40-44 weeks postconception
• In these infants, hypoxia is a potent respiratory depressant,
rather than a stimulant
• This is due either to central mediation or to changes in
respiratory mechanics
• These infants tend to develop periodic breathing or central
apnea with or without apparent hypoxia
– This is most likely because of immature respiratory control
mechanisms

Respiratory System
• During the early years of childhood,
development of the lungs continues at a
rapid pace
– This is with respect to the development of new
alveoli
• By 12-18 months the number of alveoli
reaches the adult level of 300 million or
more
– Subsequent lung growth is associated with an
increase in alveolar size

Respiratory System
• Lung volumes of infants is disproportionately small
in relation to body size
– Since the infant’s metabolic rate, in relation to body
weight, is twice that of the adult, more marked differences
are seen in respiratory frequency and in alveolar
ventilation
– The higher level of alveolar ventilation in relation to FRC
makes the FRC a less effective buffer between inspired
gases & pulmonary circulation
• Any interruption of ventilation will lead rapidly to hypoxemia &
the function of anesthetic gases in the alveolus will equilibrate
with the inspired fraction more rapidly than occurs in adults

Respiratory System
• Functional Residual Capacity (FRC)
– Determined by the balance between the
outward stretch of the thorax & the inward
recoil of the lungs
• In infants, outward recoil of the thorax is very low
– They have cartilaginous chest walls that make their chest
walls very compliant & their respiratory muscles are not
well developed
• Inward recoil of the lungs is only slightly lower than
that of an adults

Respiratory System
• The FRC of young infants in conditions such as
apnea , under general anesthesia and/or in
paralysis decrease to 10-15% of TLC
– Total Lung Capacity (TLC) is normally ~50% of an
adults
– 10-15% TLC is incompatible with normal gas exchange
because airway closure, atelectasis &
ventilation/perfusion imbalance result
• Awake infants are normally as capable of maintaining FRC as
older children & adults
– This is important because it limits O2 reserve during
apnea and greatly reduces the time before you see a
drop in oxygen saturation

Respiratory System
• Breathing Patterns of Infants
– Less than 6 months of age
• Predominantly abdominal (diaphragmatic) and the rib cage
(intercostal muscles) contribution to tidal volume is relatively
small (20-40%)
– After 9 months of age
• The rib cage component of tidal volume increases to a level
(50%) similar to that of older children & adolescents, reflecting
the maturation of the thoracic structure
– By 12 months
• Chest wall compliance decreases
• The chest wall becomes stable & can resist the inward recoil of
the lungs while maintaining FRC
• This supports the theory that the stability of the respiratory
system is achieved by 1 year of age

Anatomic Differences in the
Respiratory System
• Anatomic Airway Differences are Many
• Upper Airway: the nasal airway is the primary
pathway for normal breathing
– During quiet breathing the resistance through the nasal
passages accounts for more than 50% of the total
airway resistance (twice that of mouth breathing)
– Except when crying, the newborns are considered
“obligate nose breathers”
• This is because the epiglottis is positioned high in the pharynx
and almost meets the soft palate, making oral ventilation
difficult
– If the nasal airway becomes occluded the infant may
not rapidly or effectively convert to oral ventilation
• Nasal obstruction usually can be relieved by causing the infant
to cry

Respiratory System
• The Tongue: is large & occupies most of
the cavity of the mouth & oropharynx
– With the absence of teeth, airway obstruction
can easily occur
– The airway usually can be cleared by holding
the mouth open and/or lifting the jaw
– An oral airway may also be helpful

Respiratory System
• Pharyngeal Airway: is not supported by a
rigid bony or cartilaginous structure
– Is easily collapsed by:
• The posterior displacement of the mandible during
sleep
• Flexion of the neck
• Compression over the hyoid bone
– Chemoreceptor stimuli such as hypercapnia &
hypoxia stimulate the airway dilators
preferentially over the stimulation of the
diaphragm so as to maintain airway patency

Respiratory System
• Laryngeal Airway: this maintains the airway &
functions as a valve to occlude & protect the lower
airway
– In the infant the larynx is located high (anterior &
cephlad) opposite C-4 (adults is C-6)
– The body of the hyoid bone is between C2-3 & in the
adult is at C-4
– The high position of the epiglottis & larynx allows the
infant to breathe & swallow simultaneously
• The larynx descends with growth
• Most of this descent occurs in the 1st year but the adult
position is not reached until the 4th year
– The vocal cords of the neonate are slanted so that the
anterior portion is more caudal than the posterior

Respiratory System
• Laryngeal Reflex: is activated by stimulation of
receptors on the face, nose & upper airways of the
newborn
– Reflex apnea, bradycardia & laryngospasm may occur
– Various mechanical stimuli can trigger response
including:
• Water
• Foreign bodies
• Noxious gases
– This response is very strong in newborns

Respiratory System

Respiratory System
• Narrowest area of the airway
– Adult is between the vocal cords
– Infant is in the cricoid region of the larynx
• The cricoid is circular & cartilaginous and consequently not
expansible
• An endotracheal tube may pass easily through an infants vocal
cords but be tight at the cricoid area
– The limiting factor here becomes the cricoid ring
– This is also frequently the site of trauma during intubation
• 1mm of edema on the cross sectional area at the level of the
cricoid ring in a pediatric airway can decrease the opening
75% vs. 19% in an adult
• There should be an audible air leak at 15-20cm H2O airway
pressure when applied

Respiratory System
• Trachea
– Infant: the alignment is directed caudally &
posteriorly
– Adult: it is directed caudally
• Cricoid pressure is more effective in
facilitating passage of the endotracheal tube
in the infant

Respiratory System
• Newborn Trachea
– Distance between the bifurcation of the trachea
& the vocal cords is 4-5cm
• Endotracheal tube (ETT) must be carefully
positioned & fixed
• Because of the large size of the infant’s head the tip
of the tube can move about 2cm during flexion &
extension of the head
• It is extremely important to check the ETT
placement every time the baby’s head is moved

Respiratory System
• Tonsils & Adenoids
– Grow markedly during childhood
• Reach their largest size at 4-7 years & then recedes
gradually
• This can make visualization of the larynx more
difficult

Respiratory System
• The compliant nature of the major airways of the
infant are also different than adults
– The diameter of infant airways changes more easily
when exposed to distending or compressing forces
• With obstruction at the level of the larynx, stridor will be heard
mainly on inspiration
• With obstruction at the level of the trachea (foreign body),
stridor may be heard during both inspiration & expiration
• In contrast, during lower airway obstruction (asthma or
bronchiolitis), most of the collapse occurs during expiration
thus producing expiratory wheeze

Respiratory System
• The configuration of the thoracic cage
differs in the infant & adult
– Infant: ribs are horizontal & do not rise as much
as an adult’s during inspiration
• The diaphragm is more important in ventilation &
the consequences of abdominal distention are much
greater
• As the child grows (learns to stand) gravity pulls on
the abdominal contents encouraging the chest wall
to lengthen
– Now the chest cavity can be expanded by raising the ribs
into a more horizontal position

Respiratory System
• Lower Airway
– Diaphragmatic & intercostal muscles of infants are
more liable to fatigue than those of adults
• This is due to a difference in muscle fiber type
– Adult diaphragm has 60% of type I: slow twitch, high oxidative,
fatigue resistant
– Newborns diaphragm has 75% of type II: fast twitch, low
oxidative, less energy efficient
– The same pattern is seen in intercostal muscles
• The newborn is more prone to respiratory fatigue & may not be
able to cope when suffering from conditions that result in
reduced lung compliance (RDS)

Respiratory System
• Ventilation/Perfusion Ratio (V/Q)
– Infants & children: the distribution of
pulmonary blood flow is more uniform than
adults
• Adults changes from base to apex because of gravity
• Infants & children PAP is relatively high & the
effect of gravity is less

Respiratory System
• V/Q changes in anesthesia
– General anesthesia (GA)
• FRC & diaphragmatic movements are reduced
• Airway closure tends to be exaggerated & the
dependent parts of the lung are poorly ventilated
• Hypoxic pulmonary vasoconstriction, which diverts
blood flow from areas of the lung that are under
ventilated, is abolished during GA
– This increases the hypoxic tendency

Respiratory System
• In General:
– Rate & depth of respiration are regulated to
expend the least amount of energy
– At their given rates, both the infant & the adult
expend about 1% of their metabolic energy in
ventilation

Respiratory System
• Periodic Breathing
– Can be observed in the normal newborn infant
& frequently occurs during REM sleep
– Manifested as rapid ventilation followed by a
period of apnea of less than 10secs
• During this period arterial oxygenation tension
remains in the normal range
– Usually not seen in healthy infants after 6
weeks of age

Respiratory System
– Apneic spells longer than 20secs are frequently
seen in premature infants & are frequently
associated with arterial desaturation &
bradycardia
• Episodes of apnea increase in frequency during
stressful situations such as respiratory infection or
the postanesthetic & postsurgical states
• Apneic spells can be central (originating in the
CNS) or obstructive (d/t upper airway obstruction)
• Treatment with caffeine & theophylline has been
show to be effective in reducing both types in
preterm infants

Respiratory System
• Tidal Volume
– 7-10ml/kg
• Dead Space
– 2-2.5ml/kg
• These two measures
remain constant
between infants &
adults

Oxygen Transport
• Blood volume of a healthy newborn is 70-90ml/kg
• Hemoglobin tends to be high (approx. 19g/dl)
– Consisting primarily of HgF
– Hgb rises slightly in the first few days because of the
decrease in extracellular fluid volume
• Thereafter, it declines & is referred to as physiologic anemia of
infancy
– HgF has a greater affinity for oxygen than HgA
– After birth, the total Hgb level decreases rapidly as the
proportion of HgF diminishes (it can drop below 10g/dl at
2-3 months) creating the anemia

Oxygen Transport
– The P-50 rapidly increases at the same time the HgF is
replaced by HgA which has a high concentration of 2,3-
DPG & so insures efficient oxygen off-loading at the
tissues
• The gradual decrease in O2 carrying capacity in the first few
months of life is thus well tolerated by normal, healthy infants
– There is no consensus about the lowest tolerable Hgb
concentration for an infant
• The lowest limit will depend on factors such as duration of
anemia, the acuity of blood loss, the intravascular volume &
more important the impact of other conditions that might
interfere with O2 transport

Key Points
• Respiratory control mechanisms are not
fully developed until 42-44 weeks
postconception
• Most alveolar formation & elastogenesis
occurs during the first year of life
– The thoracic structure is insufficient to support
the negative pleural pressure during the
respiratory cycle until the infant develops
muscle strength from upright posture around 1
year old

Key Points
• Weakness of the thoracic structure is partly
compensated for by contractions of the intercostal &
accessory muscles
– Anesthesia abolishes this compensatory mechanism & the
end expiratory lung volume (FRC) decreases to the point
of airway closure & alveolar collapse
• Infants are prone to upper airway obstruction
– Due to anatomic & physiologic differences
– Anesthesia depresses pharyngeal & other neck muscles
which resist the collapsing forces in the pharynx

Key Points
• HgF has high oxygen affinity & limits
oxygen unloading at the tissue level
– This decreases O2 delivery to the tissues that
have high oxygen demand
– Infants & young children are prone to
perioperative hypoxemia & tissue hypoxia

Airway Management
• The technique of endotracheal intubation in the
neonate & small infant differs from that in the
adult because of the baby’s anatomical features
– The large head & short neck may necessitate the need
for a shoulder roll
– The angle of the jaw is about 140° (adult is 120°)
– The epiglottis is more “U” shaped, usually resembling
the Greek letter omega
• The epiglottis also protrudes over the larynx at a 45° angle
– The larynx of an infant is high & has an anterior
inclination
• Straight (Miller or Phillips) blade is usually the best choice
• The view can be markedly improved by applying cricoid
pressure

Airway Management
• Selection of Endotracheal Tube Size
– Diameter
• Greater than 2 years old
– In millimeters=Age+16÷4
– In french=Age+18
• 12-24 months=4.0
• 6-12 months=3.5-4.0
• Newborn-6 months=3.0-3.5
• Premie=2.0-3.0
– Cuffed tubes
• After 8 years old add 2 Fr. sizes to diameter

Airway Management
• Distance or Depth to
Tape Tube
– If older than 2 years
• Age÷2+12
– If younger than 2 years
• 1-2-3-4 kg then it is
taped at 7-8-9-10cm
respectively
• Newborn to 6 months =
10cm
• 6 to 12 months = 11cm
• 1 to 2 years = 12cm

Renal Differences
• Body Fluid
Compartments
– Full term infants have
a large % of TBW &
ECF
– TBW decreases with
age mainly as a result
of loss of water in
extracellular fluid

Renal Differences
• Significance for Anesthesia Provider
– Higher dose of water soluble drug is needed
due to the greater volume of distribution
• However, due to the immaturity of clearance &
metabolism the dose given is equal to the dose used
in adults
– In the fetus the placenta is the excretory organ
• However, it still produces a large volume of
hypotonic urine & helps amniotic fluid volume
• It is only after birth that the kidney begins to
maintain metabolic function

Renal Differences
• The healthy newborn has a complete set of
nephrons at birth
– The glomeruli are smaller than adults
– The filtration surface related to body weight is
similar
– The tubules are not fully grown at birth & may
not pass into the medulla

Renal Differences
• Glomerular Filtration Rate (GFR)
– At birth is ~30% of the adult
• It increases quickly during the first two weeks, but then is
relatively slow to approach the adult level by the end of the
first year
– Low GFR in the full term infant affects the baby’s
ability to excrete saline & water loads as well as drugs
• Full term infants can conserve Na+, as GFR increases so does
the filtered load of Na+ increase & the ability of the proximal
tubule to reabsorb the ion
• In premature infants a glomerulotubular imbalance is present
which may result in Na+ wastage & hyponatremia

Renal Differences
– Factors that contribute to the increase in GFR
• Increase in CO
• Changes in renovascular resistance
• Altered regional blood flow
• Changes in the glomeruli
– Maturation of the glomerular function is
complete at 5-6 months of age

Renal Differences
• Tubular Function & Permeability
– Not fully mature in the term neonate & even less in the
premature infant
– The neonate can excrete dilute urine (50mOsm/L)
• However, the rate of excretion of H2O is less & it cannot
concentrate to more than 700mOsm/L (adult, 1200mOsm/L)
• This is due, in part, to the lack of urea-forming solids in the diet,
but mostly due to the hypotonicity of the renal medulla
– Maturation of the tubules is behind that of the glomeruli
• Peak renal capacity is reached at 2-3 years after which it decreases
at a rate of 2.5% per year

Renal Differences
• The kidney does show some response to
antidiuretic hormone (ADH), but is less sensitive
to ADH than the cells of mature nephrons
• Diluting Capacity
– Matures by 3-5 weeks postnatal age
– The ability to handle a water load is reduced & the
neonate may be unable to increase water excretion to
compensate for excessive water intake
• They are very sensitive to over hydration
– In infants & children, hyponatremia occurs more
frequently than hypernatremia

Renal Differences
• Creatinine
– Normal value is lower in infants than in adults
• This is due to the anabolic state of the newborn & the small
muscle mass relative to body weight (0.4mg/dl vs. 1mg/dl in
the adult)
• Bicarbonate (NaHCO3)
– Renal tubular threshold is also lower in the newborn
(20mmol/L vs. 25mmol/L in the adult)
– Therefore, the infant has a lower pH, of about 7.34
• BUN
– The infants urea production is reduced as a result of
growth & so the “immature” kidney is able to maintain
a normal BUN

Hepatic Differences
• Glucose from the mother is the main source of
energy for the fetus
– Stored as fat & glycogen with storage occurring mostly
in last trimester
• At 28 weeks gestation the fetus has practically no fat stored,
but by term 16% of the body is fat & 35gms of glycogen is
stored
– In utero liver function is essential for fetal survival
• Maintains glucose regulation, protein / lipid synthesis & drug
metabolism
• The excretory products go across the placenta & are excreted
by the maternal liver
– Liver volume represents 4% of the total body weight in
the neonate (2% in adult)
• However, the enzyme concentration & activity are lower in the
neonatal liver

Hepatic Differences
• Glucose is the infants main source of energy
– In the 1st few hours following delivery there is a
rapid drop in plasma glucose levels
• Hepatic & glycogen stores are rapidly depleted with
fat becoming the principle source of energy
• The newborn should not be kept for a long period of
time from enteral or IV nutrition
– The lower limit of normal for glucose is 30mg/dl in the
term infant
– Infants do not usually show neurological signs &
symptoms, but may develop sweating pallor or tachycardia
– A glucose level < 20mg/dl usually precipitates
neurological signs such as apnea or convulsions
– Premature infants may have a tendency for hypoglycemia
for weeks

Hepatic Differences
• Increased hepatic metabolic activity
– Occurs at about 3 months of age
– Reaches a peak at 2-3 years by which time the
enzymes are fully mature, then they start to
decline reaching adult values at puberty
• Renin, angiotensin, aldosterone, cortisol &
thyroxine levels are high in the newborn &
decrease in the first few weeks of life

Hepatic Differences
• Physiologic Jaundice
– Increased concentrations of bilirubin occur in
the first few days of life
• This is excessive bilirubin from the breakdown of
red blood cells & deficient hepatic conjugation due
to immature liver function
• Treatment is phototherapy & occasionally exchange
transfusions
• If left untreated it can lead to encephalopathy
(kernicterus)

Hepatic Differences
• Coagulation
– At birth, Vit K dependent factors (II, VII, IX &
X) are at a level of 20-60% of the adult volume
• This results in prolonged prothrombin times
– Synthesis of Vit K dependent factors occurs in
the liver which being immature leads to
relatively lower levels of these factors even
with the administration of Vit K
• It takes several weeks for the levels of coagulation
factors to reach adult values
• Administration of Vit K immediately after birth is
important to prevent hemorrhagic disease

CNS Differences
• The brain of the neonate is relatively large
– 1/10 of the weight as compared to 1/50 of adult
– The brain grows rapidly
• Doubles in weight by 6 months
• Triples in weight by 1 year
– At birth ~25% of the neonatal cells are present
– By one year the development of cells in the
cortex & brain stem is complete

CNS Differences
• Myelination & Elaboration of Dendritic
Processes
– Continue into the third year of life
– Incomplete myelinization is associated with
primitive reflexes such as motor and grasp
• Spinal Cord
– At birth the spinal cord extends to L-3
– By one year old the infant spinal cord has
assumed its permanent position at L-1

CNS Differences
• Structure & Function of the Neuromuscular
System
– Incomplete at birth
• There are immature myoneural junctions & larger
amount of extrajunctional receptors
– Throughout Infancy:
• Contractile properties change
• The amount of muscle increases
• The neuromuscular junction & acetylcholine
receptors mature

CNS Differences
• Junctions & Receptors
– The presence of immature myoneural junctions
might cause a predisposition to sensitivity
– A large number of extrajunctional receptors
might result in resistance
– Within a short interval, (< 1 month) this
variation diminishes & the myoneural junction
of the infant behaves almost like that of an
adult

Temperature Regulation
• Body Temperature
– Is a result of the balance between the factors
leading to heat loss & gain and the distribution of
heat within the body
• The potential exists for unstable conditions to progress
to a positive feedback cycle
– The decrease in body temperature will lead to a decrease in
the metabolic rate, leading to further heat loss & diminished
metabolic rate
• The body normally safeguards against this unstable
state by increasing BMR during the initial exposure to
cold or by reducing heat loss through vasoconstriction

• Central Temperature Control Mechanism
– This is intact in the newborn
• It is limited, however, by autonomic & physiologic
factors
• Is only able to maintain a constant body temperature
within a narrow range of environmental conditions
• O2 consumption is at a minimum when the
environmental temp is within 3-5% (1-2°C) of body
temp (an abdominal skin temp of 36°C)
– This is known as the neutral thermal environment (NTE)
– A deviation in either direction from the NTE will increase
O2 consumption
– An adult can sustain body temperature in an environment
as cold as 0°C where as a full term infant starts developing
hypothermia at about 22°C

• Generation of Heat
– Depends mostly on body mass
• Heat loss to the environment is mainly due to
surface area
• Neonates have a ratio of surface area to mass about
3X’s higher than that of adults
– Therefore they have difficulty regulating body temperature
in a cold environment

• Premature Infants & Temperature Control
– Are more susceptible to environmental changes
in temperature
– The preemie has skin only 2-3 cells thick & has
a lack of keratin
• This allows for a marked increase in evaporative
water loss (in extremes this can be in excess of heat
production)

• Important Mechanisms for Heat Production
– Metabolic activity
– Shivering
– Non-shivering thermogenesis
• Newborns usually do not shiver
– Heat is produced primarily by non-shivering
thermogenesis
• Shivering does not occur until about 3 months of
age

• Non-shivering Thermogenesis
– Exposure to cold leads to production of Norepi
• This in turn increases the metabolic activity of
brown fat
• Brown fat is highly specialized tissue with a great
number of mitochondrial cytochromes (these are
what provide the brown color)
• The cells have small vacuoles of fat & are rich in
sympathetic nerve endings
– They are mostly in the nape & between the scapulae but
some are found in the mediastinal (around the internal
mammary arteries & the perirenal regions (around the
kidneys & adrenals)

– Once released Norepi acts on the alpha & beta
adrenergic receptors on the brown adipocytes
• This stimulates the release of lipase, which in turn splits
triglycerides into glycerol & fatty acids, thus increasing
heat production
• The increase in brown fat metabolism raises the
proportion of CO diverted through the brown fat
(sometimes as much as 25%), which in turn facilitates
the direct warming of blood
– The increased levels of Norepi also causes
peripheral vasoconstriction & mottling of the skin

• Heat Loss
– The major source of heat loss in the infant is
through the respiratory system
• A 3kg infant with a MV of 500ml spends 3.5cal/min
to raise the temperature of inspired gases
• To saturate the gases with water vapor takes an
additional 12cal/min
• The total represents about 10-20% of the total
oxygen consumption of an infant

– The sweating mechanism is present in the
neonate, but is less effective than in adults
• Possibly because of the immaturity of the
cholinergic receptors in the sweat glands
• Full term infants display structurally well developed
sweat glands, but these do not function appropriately
• Sweating during the first day of life is actually
confined mostly to the head

• Heat Exchange Review
– 1. Conduction:
• The kinetic energy of the vibratory motion of the
molecules at the surface of the skin or other exposed
surfaces is transmitted to the molecules of the
medium immediately adjacent to the skin
– Rate of transfer is related to temperature difference
between the skin & this medium
– Use warm blankets, Bair huggers & warmed gel pads
– 2. Convection:
• Free movement of air over a surface
– Air is warmed by exposure to the surface of the body then
rises & is replaced by cooler air from the environment
– Increase OR temp, radiant warmers, wrap in saran wrap,
cover with blankets and/or OR drapes

– 3. Radiation:
• Radiation emitted from the body is in the infrared region
of the electromagnetic spectrum
– The quantity radiated is related to the temperature of the
surrounding objects
– Radiation is the major mechanism of heat loss under normal
conditions (same techniques to prevent as used in Convection)
– 4. Evaporation:
• Under normal conditions ~20% of the total body heat
loss is due to evaporation
– This occurs both at the skin & lungs
– Since the infant’s skin is thinner & more permeable than the
older child’s or adult’s evaporative heat loss from the skin is
greater
– In the anesthetized infant the MV (relative to body weight) is
high thus increasing evaporative heat loss through the
respiratory system

• Summary
– Decreased body temperature is initially
compensated for by increased metabolism
– If this fails & temperature continues to
decrease, regional blood flow shifts, causing a
metabolic acidosis & eventually apnea

Pharmacological Differences
with Inhalation Anesthetics
• Review
– Factors that determine uptake & distribution of
inhaled agents
• Factors that determine the rate of delivery of gas to
the lungs
– Inspired concentration
– Alveolar ventilation
– FRC
• Factors that determine the rate of uptake of the
anesthetic from the lung
– CO
– Solubility of the agent
– Alveolar-to-venous partial pressure gradient

• In children there is a more rapid rise from
inspired partial pressure to alveolar partial
pressure than in adults
– This is due to 4 differences between children &
adults
• 1. The ratio of alveolar ventilation to FRC
– This a measure of the rate of “wash-in” of the anesthetic
into the alveoli
– In the neonate the ration is 5:1 compared to adults of 1.5:1

• 2. There is a higher proportion of CO distributed to
the VRG in the child
– In adults an increase in CO slows the rate of rise in
alveolar to inspired partial pressure, but in neonates it
speeds the rate of induction because the CO is
preferentially distributed to the VRG
– The VRG constitutes 18% of the body weight of the
neonate as opposed to only 6% in adults
– Therefore, the partial pressure in the VRG (which includes
the brain) equilibrates faster with the alveolar partial
pressure

• 3. Neonates have a lower blood/gas solubility of
inhaled anesthetics (the less soluble the greater the
amount that remains in the alveolus
– This allows a more rapid rise in the alveolar to inspired
partial pressure
• 4. Neonates have a lower tissue/blood solubility of
inhaled anesthetics
– Less agent is removed from the blood therefore the partial
pressure of the agent in the blood returning to the lungs
increases

•There are age related differences in MAC of inhalation
agents

Pediatric anatomy, physiology & pharmacology

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Pediatric anatomy, physiology & pharmacology

Similar to Pediatric anatomy, physiology & pharmacology (20)

More from Rohit Paswan

More from Rohit Paswan (20)

Recently uploaded

Recently uploaded (20)

Pediatric anatomy, physiology & pharmacology