neonatal physiology

Dr shibinath V M

Appreciate physiological changes which take place following birth and the unique aspects of neonatal physiology including:

1)limited reserve capacity for temperature control, cardiovascular and respiratory function

2)variable and individualized fluid requirements

3) implications of hepatic and renal immaturity

NEWBORN-first 24 hrs of life

NEONATE-from birth to under four weeks(<28 days)

TERM NEONATE-between 37 to < 42 gestational weekPRETERM NEONATE-<37 gestational week irrespective ofBWPOST TERM NEONATE-> or egual to 42 gestational week

LOW BIRTH WEIGHT(LBW)<2500 GRAM VERY LOW BIRTH WEIGHT(VLBW)<150O GRAMEXTREMELY LOW BIRTH WEIGHT(ELBW)< 1000 GRAM

BW

IUGR (Intrauterine growth restriction);- refers to a condition in which a foetus is unable to achieve its genetically determined potential size.

AIM

Oxygenated placental blood is preferentially delivered to the brain,myocardium and upper torsolower oxygen tension blood distributed to the lower body and placenta Preferential splitting is achieved via intra- and extracardiac shunts that direct blood into two parallel circulations (the left ventricle providing 35% and the right 65% of cardiac output. )

Fetal cardiacoutput is therefore measured as a combined ventricular output closure of the intracardiac (foramen ovale) and extracardiac shunts (ductus venosus and ductus arteriosus)

Oxygenated blood via umbilical vein either through the liver or via the ductus venosus to reach IVC

blood remains on the posterior wall of the inferior vena cava, allowing it to be directed across the foramen ovale into the left atrium by the Eustachian valve

blood passes left ventricle and aorta to supply the head and upper torso.

deoxygenated blood returning from the SUPERIOR vena cava and myocardium via the coronary sinus is directed through the right ventricle and into the pulmonary artery.

Most of this blood is returned to the descending aorta via the ductus arteriosus; ( 8-10%of total cardiac output passes through the high-resistance pulmonary circulation.)

Blood in the descending aorta either supplies the umbilical artery to be reoxygenated at the placenta or continues to supply the lower limbs.

UMBILICAL VESSELS- IMMEDIATELY AFTER CLAMPING: constrict in response to stretching and increased oxygen content at delivery large low-resistance placental vascular bed removed from the circulationincrease SVRReduction of blood flow along ductus venosus (passive closure over the following 3-7 days),reduced blood flow in IVC

Lung expansiondrops pulmonary vascular resistance increase in blood returning to the LA These two changes reduce right atrial and increase left atrial pressures, functionally closing the foramen ovale within the first few breaths of life

Successful transition from foetal to postnatal circulation requires

clamping of umbilical cord and removal of the placenta

increased pulmonary blood flow,

Shunt closure

1. Pressure in RA decreases

2. Blood flows to the lungs

4. Pressure in the LA increases RT Flow of blood from the lungs

3. Ductus Arteriosusbegins to constrict

5. Increase pressurein the LA forcesthe foramen ovale to close

physiological reverse shunt from left to right commonly occurs.

FORAMEN OVALE completely closed in 50% of children by 5 years remains probe patent in 30% of adults, can facilitate paradoxical embolus and potential stroke.

DUCTUS ARTERISUS- Th e ductus arteriosus has functionally (but not anatomically)

closed in 58% of normal full-term infants by 2 days of life and in 98% by day

4. drop in pulmonary artery pressure and increase in SVR reverses

flow across the ductus arteriosus from L TO R affected by blood oxygen content circulating prostaglandins. E2 .

With ligation of the umbilical vein, portal pressure

falls, triggering closure of the ductus venosus. This process rarely requires more than 1 to 2 weeks. which becomes the ligamentum venosum

DUCTUS VENOSUS

median umbilical ligament, a different structure that represents the remnant of the embryonic urachus.

umbilical arteries-- Medial umbilical ligamenton the deep surface of the anterior abdominal wall

Left Umbilical Vein - Ligamentum Teres Of Liver

Right Umbilical Vein – Disappears

DUCTUS ARTERIOSUS- ligamentum ateriosum

IMPORTANT-

stimulus such as hypoxia, acidaemia or structural anomaly can increase pulmonary vascular resistance and potentially re-open the ductus arteriosus or foramen ovale. which allows a right-to-left shunt, which worsens hypoxia

.Eg seen in persistent pulmonary hypertension of the newborn.

term neonatal cardiac output is approximately 200 ml/kg/minute

fewer myofibrils in a disordered pattern,

Less mature sarcoplasmic reticulum and trans tubular system

Dec . CA-ATP ACTIVITY, dependent on exogenous ionized calcium

follows the Franke Starling relationship of filling pressure to stroke volume, but on a much flatter section of the curve compared with adults. i.e limited increase in stroke volume for a given increase in ventricular filling volume.

dependent on heart rate to increase cardiac output and cardiac output can respond to increased ventricular filling.

parasympathetic nervous system more developed than sympathetic

Ventricular maturation and associated ECG changesThe fetal heart - right-side dominant, with the right ventricleresponsible for 65% of cardiac output in utero. The neonatal ECG reflects RAD R wave dominance in lead V1S wave dominance in lead V6.

At 3-6 months the classical LAD pattern established as ventricular hypertrophy occurs in response to increased systemicvascular resistance

Left ventricle has high tone has limited contractile reserve due to;-

Reduced no of alpha receptorsHigh level of circulating catecholaminesLimited recruitable stroke volumeImmature calcium transport systemDec ventricular complianceeffect of parasympathetic nervous system is more predominantBeta adrenergic receptors are more developed than alpha thus respond better to dobutamine and isoproterenol

neonates can tolerate hypoxia better due toHigh concentration of glycogenMore effective utilisation of anaerobic metabolismHence can be resusitated easily if oxygenation and perfusion are reestablished

Oxygen consumption increases after birth(at neutral temperature )Full term childAt birth-6ml/kg/min10 days-7 ml/kg/min4 week-8 ml/kg/min

Chemical

Sensory/ Thermal

Mechanical InitiationInitiation ofof BreathingBreathing

Compression of fluid from the fetal lung during vaginal delivery establishes the lung volume

Negative inspiratory pressures of up to 70-100 cm H2O are initially required to expand the alveoli which facilitate lung expansion by overcoming: airways resistance inertia of fluid in the airways surface tension of the air/fluid interface in the alveolus

As the chest passes through the birth canal the lungs are compressed

Subsequent recoil of the chest wall produces passive inspiration of air into the lungs

1. With cutting of the cord, remove oxygen supply 2. Asphyxia occurs

3. CO2 and O2 and pH = ACIDOSIS

4. Acidotic state-- stimulates the respiratory center in the medulla and the chemoreceptors in carotid artery to initiate breathing

Thermal--the decrease in environmental temperature after delivery is a major stimulus of breathing

Tactile--nerve endings in the skin are stimulated

Visual--change from a dark world to one of light

Auditory--sound in the extrauterine environment stimulates the infant

1)Alveolar distension, cortisol and epinephrine further stimulate type II pneumocytes to produce surfactant

2)Expiration initially active,pressures of 18-115 cm H2O generatedamniotic fluid forced out from the bronchi.

PHYSIOLOGICAL CHANGES LEAD TO-increasing blood flow and initiating the cardiovascular changes

.

ALVEOLAR DEVELOPMENTContinues even after birthAt birth 24 million alveoli300 million by 8 years of ageInitially increases in no ,further increase by inc in size and airway development

Lungs develop from the third week of gestation with completion of the terminal bronchioles by week 16

SURFACTANT type I and II pneumocytes are distinguishable only by 20-22 weeks present only after 24 weeks,

production can be increased after 24 weeks by giving betamethasone to the mother, thereby improving neonatal lung function if premature delivery is anticipated

APPLIEDseen preterm babies decreases the compliance – risk for respiratory distress syndrome, bronchopulmonary dysplasia and pulmonary hypertension

.

Diaphragm-two types of fibres

Type 1-slow twitch, highly oxidative ,sustained contraction ,less fatigueType 2-fast twitch, low oxidative ,quick contraction and easily fatigued

New born have 25% TYPE-1,(PRETERM 10%),BY AGE OF TWO YRS 55%APPLIED-risk of diaphragmatic fatigue during hyperventilation

Large occiput-more flexion may lead to obstruction Larynx is funnel shaped narrowest portion is cricoid –uncuffed tube

preferred(micro cuff useful ,costly) Large size of the tongue-increases chances of

obstruction and difficult laryngoscopy Higher level of larynx(c3 in preterm,c4 in term and

c5-c6 in adults)-straight blade more useful Epiglottids- short,stubby,omega shaped, angled over

laryngeal inlet-control with laryngeal blade more difficult

Tip of epiglottids lies at c1,with close apposition with soft palate-allows simultaneously sucking and breathing

Vocal cords angled-blind intubation ,tube may lodge at anterior commisure

Chest wall development

Ribs oriented parallel and unable to increase the thoracic volume during inspiration

At 2 yrs old associated with standing and walking, ribs are oriented oblique

Cartilaginous structure with inward movement during inspiration

imbalance exists between chest wall rigidity and elastic recoil of neonatal lungs. (CONTAIN IMMATURE ELASTIC FIBRES,thus tendency to recoil)

increase closing capacity to the point of exceeding functional residual capacity (FRC) until the age of 6. To counteract this, neonates produce positive end expiratory pressure(PEEP) via high resistance nasal airways and partial closure of the vocal cordsLimited Inspiratory reserve volume Minute volume is maintained by high respiratory rateRespiratory fatigue common

Neonatal lung mechanics-gas exchange immature in neonates, total shunt estimate of 24% of the cardiac output at birth, reducing to 10% of cardiac output at 1 week. rapid reduction in shunt fraction improves arterial oxygenation and reduces the effort of breathing.

implications during anaesthesia. effective FRC is reduced( physiological PEEP and intercostal muscle tone is lost) along with an increased shunt fraction and High metabolic rate (6-8ml ofO2/kg/minute), These factors contribute to a potential rapid desaturation in neonates under anaesthesia.

Control of ventilation Peripheral chemoreceptors functional at birth but are initially silent because of high post delivery blood oxygen content.Receptor adaptation occurs over 48 hours,

APNOEA OF PREMATURITYneonates exhibit periodic breathing pattern defined as an apnoea of less than 5 seconds often followed by tachypnoea.,

Premature neonates exhibit apnoeic episodes of more than 15 seconds or a shorter period a/w fall in heart rate due to loss of central respiratory drive improves with maturity may persist up to 60 weeks postconceptual ageAnaemia i.e. haematocrit<30% is any independent risk factor

characterized by biphasic response 1)an initial increase in ventilation followed by a decrease in ventilation; 2).much rapid than adults due to low resting carbon dioxide

Response Varies with temperature, level of arousal and maturity

.

PATHOPHYSIOLOGYhypoxia, acidosis and inflammatory mediators l/t persistent increase in pulmonary artery pressure persistent fetal circulationPpt condition-birth asphyxia,meconium aspiration sepsis,CDH, maternal use of nsaids,GDM,,casearen deliveryLeads to R TO L shunt resulting in profound hypoxia,with elevated PCO2

Persistent fetal circulation, this phenomenon may produce life-threatening hypoxemia that may require inhaled nitric oxide or extracorporeal support (i.e., extracorporeal membrane oxygenation)to fulfill the placental role and sustain life

Goal-PaCO2-50 TO 55mmhg and Pao2-50-70 mmhgMANAGEMENT:-1)treat precipitating condition eg hypoxia,hypoglycemia2)Inhaled nitric oxide3)Mechanical ventilation4)high frequency ventilation 5)exogenous steroids6)inhaled steroid7)ECMO8)experimental-slidnafil

Marker for chronic hypoxia in utero in third trimester due to interferance in maternal circulation

passage of meconium in utero-fetus breathes in meconium mixed amniotic fluid enters in pulmonary circulation

Leads to varying degree of respiratory distress Increase in amount of amount of musle in blood vessels of

distal respiratory units

“If the baby is not vigorous (Apgar 1-3): Suction the trachea soon after delivery (before many respirations have occurred) for ≤ 5 seconds. If no meconium retrieved, do not repeat intubation and suction. If meconium is retrieved and no bradycardia present, reintubate and suction. If the heart rate is low, administer PPV and consider repeat suctioning. “

“If the baby is vigorous (Apgar >5): Clear secretions and meconium from the mouth/nose with a bulb syringe or a large-bore suction catheter. In either case, the remainder of the initial resuscitation: dry, stimulate, reposition, and administer oxygen as necessary.”

75% of TBW,80-85% IN PRETERMReduced to 60-65% BY one yearECF:ICF IS 2:1,The diuresis reduces the extracellular water (30% of TBW) and ICF increases due to growth of cellls-reaches adult value by 1 yr

Blood volume Full term-85 ml /kg Preterm90-100 ml /kg(50 ml/kg is plasma)

The maintenance need for water in parenteral fluid therapy- were provided byHolliday and Segar in 1957

‘insensible loss of water and urinary water loss roughly parallel energy metabolism and do not parallel weight’

In the fi rst few days of life, isotonic losses of salt and water cause the normal neonate to lose 5% to 15% of its body weight.

1. 0-10 kg: 100 kcal/kg.2. 10-20 kg: 1000 kcal + 50 kcal/kg for each kg over 10 kg.3. 20 kg and up: 1500 kcal + 20 kcal/kg for each kg over 20 kg.

maintenance requirements Sodium 3.0, mEq/100 calories/dayChloride 2.0 mEq/100 calories/daypotassium 2.0 mEq/100 calories/day

Glycogen stores 100Kcal/day------from 9th month

Mostly depleted in 24-48 hr Gluconeogenesis 4mg/kg/min At birth, fetal serum glucose is 60% to

70% of maternal levels. should exceed 45 mg/dL to avoid

neurologic injury Symptoms of hypoglycemia may include

jitteriness, lethargy, temperature instability, and convulsion

Ten percent dextrose in water (D10W) may be given as a bolus of 2 to 4 mL/kg followed by a continuous infusion providing 4 to 6 mg/kg/min.

Th e serum glucose concentration is then followed every 30 minutes and the infusion titrated

Thermogregulation

2.5-3.0 times higher surface area BWlimited insulating capacity from subcutaneous fat and the inability of neonates to generate heat by shivering until 3 months of age.

Heat loss1) radiation(39%)2)convection (34%)3)evaporation (24%) and4)conduction(3%).

THERMOGENESIS1)by limb movement and2) by stimulationof brown fat (non-shivering thermogenesis).

C old Item s on Bed

Cold Walls

C old R oom T em p.

R adiation

C old Blankets

C old X -ray plates

C old Scale

C onduction

Passing T raffi c

Oxygen left on

Bed Near Air Vent

C onvection

T achypnea

Bath

Wet Diaper

E vaporation

Baby

BROWN FAT

6% of term body weight (dec in preterm)found in the interscapular region, mediastinum, axillae, vessels of the neck andperinephric fat highly vascular with sympathetic innervationhigh mitochondrial content to facilitate heat generation Non-shivering thermogenesis

.1. Skin receptors perceive a drop in

environmental temperataure2. Transmit impulses to the central nervous

system3. Which stimulates the sympathetic nervous

system4. Norepinephrine is released at local nerve

endings in the brown fat5. Metabolism of brown fat6. Release of fatty acids7. Release of HEAT!

heat loss minimized by

increasing the temperature of the surrounding environment.

CAREFUL;- the environmental temperature exceeds neonatal temperature then heat will be gained, which can be harmful as the ability to sweat is present only after 36 weeks postconceptual age.)

by warming surrounding air and minimizing air speed across the baby’s skin,

increasing ambient humidity and reducing air speed across the neonate.

Insensible water loss through the skin can be minimized by putting the preterm neonate in a plastic bag or covering the body,and especially the head

Haematology

contains both adult (HbA) and fetal haemoglobinHbF

70-80% upto 90% in pretermfour globin chains alpha2delta2 greater affinity for oxygen and helps maintain the molecular structure and function in a more acidic environmentfacilitates oxygen transfer across the placenta from maternal HbA. replaced with HbA at approximately 6 month of age.

Postdelivery,

increase in 2,3-diphosphoglycerate levels, shifting the oxygen dissociation curve to the right,

occurs in the liver in utero but is restricted to bone marrow from 6 weeks post delivery, thus limiting potential sites for haemoglobin synthesis.

PHYSIOLOGICAL ANAEMIA OF INFANCYOcccurs around 8-10 week of ageHbF is lost faster than HbA is synthesized. low levels of erythropoietin due to improved tissue oxygenation after birthdecreased lifespan of HbF-laden red blood cells relative increase in the blood volume,These factors contributes to the shrinking cellmass

Hepatic

Most enzymatic pathways are present inactive at birthbecome fully active at 3 monthsAlbumin level low-more free drug in circulationRisk of hypoglycemia-low glycogen stores and dec synthetic function

UNCONJUGATED HYPERBILIRUBINEMIA

Unconjugated bilirubin levels rise during the first 48 hours rapid breakdown of HbF poor conjugating abilities of the immature liver.exacerbated in presence of haemolysis, sepsis, dehydration or excessive bruising; can cross the blood brain barrier kernicterus and subsequent developmental delay. Bilirubin levels gradually fall over the first 2weeks, jaundice in term infants being rare beyond this period

Clotting factors1) do not cross the placenta; 2)factors V, VIII and XIII are at adult concentrations before birth.3)vitaminK-dependent clotting factors (II, VII, IX, X, protein C and S) areinitially low

# because of a lack of vitamin K stores and# immature hepatocyte function causing a prolongation in prothrombin time

.4)Platelet function diminished due to low levels of serotonin and adeninenucleotides, despite platelet counts in the adult range

VITAMIN K PROPHYLAXIS

#Breast milk is a poor source of vitamin K #Endogenous synthesis by the gut flora is not established for the first few weeksafter birth. #protect against haemorrhagic disease of the \

newborn

Renal

EXCRETORY FUNCTION1 million nephrons is present by 34 weeks ’gestation. The glomeruli and nephrons are immature at birth Low GFR and limited concentrating ability./obligate salt losing Suseptible to both dehydration and volume overloadLack of renal medulla osmotic gradient and absence of medullary tubules limit urinary concentrating ability,half that of the adult (1200-1400 mOsm/kg)Glycosuria and aminoaciduria are commonly detected because of immature active transport pumps in the proximal tubule.

ENDOCRINOLOGYRenal immaturity affects vitamin D formation and calcium homeostasis. The fetus and neonate have a high calcium and phosphate requirement for bone formation and growth.

precocious in development ,

continues to develop to achieve a full complement of cortical and brainstem cells by 1 year.

neonatal cerebral circulation receiving one-third of cardiac output compared with one-sixth of cardiac output in adults

The blood brain barrier is immature in the neonatal period

increased permeability to fat-soluble molecules

potentially increasing the sensitivity to certain anaesthetic drugs(

Cerebral autoregulation is fully developed at term, maintaining cerebral perfusion down to a mean arterial pressure of 30 mmHg, reflecting the lower blood pressures found in neonates.

ANS better developed to protect against hypertension than hypotension because the parasympathetic system predominates., reflected in the propensity of neonates to bradycardia and relative vasodilation.

Delayed myelination-easier intraneural penetration of LA,short time of onset and diluted conc as effective as concentrated

pathways are developed by 24-28 weeks’ gestation,

The concept of neonatal nociception is now widely accepted, with adultlike

physiological stress and behavioural responses to a noxious Stimulus

Neonates undergoing awake nasal intubation increase mean arterial pressure by 57% and intracranial pressure by a similar amount.

Noxious stimulus exposure in the neonatal period can also affect behavioural patterns in later childhood, suggesting adaptive behaviour and memory for previous experience

Cotes pediatric anesthesia 4th edition

Wylie Churchill-Davidson's A Practice of Anesthesia 7E

Understanding pediatric anesthesia 3rd edition-Rebecca Jacob

Miller’s anesthesia 8th edition

Small for Gestational AgeWhat is small for gestational age (SGA)?Small for gestational age is a term used to describe a baby who is smaller than the usual amount for the number of weeks of pregnancy. SGA babies usually have birthweights below the 10th percentile for babies of the same gestational age. This means that they are smaller than many other babies of the same gestational age.

SGA babies may appear physically and neurologically mature but are smaller than other babies of the same gestational age. SGA babies may be proportionately small (equally small all over) or they may be of normal length and size but have lower weight and body mass. SGA babies may be premature (born before 37 weeks of pregnancy), full term (37 to 41 weeks), or post term (after 42 weeks of pregnancy).

Ductus Arteriosus - Ligamentum Arteriosum

Ductus Venosus - Ligamentum Venosum

Left Umbilical Vein - Ligamentum Teres Of Liver

Right Umbilical Vein – Disappears

Vitellointestinl Duct-meckel's Diverticulum

Urachus -median Umbilical Ligament

Proximal Part Of Umbilical Artery-superior Vesical Artery

Distal Part Of Umbilical Artery-lateral Umbilical Ligament

Left Common Cardinal Vein-oblique Vein Of Left Atrium

Active acquired immunityPregnant woman forms antibodies herself

Passive acquired immunityMom passes antibodies to the fetusLasts for 4-8 months

Newborn begins to produce own immunity about 4 weeks of age