NEONATAL PHYSIOLOGY AND TRANSITION PERIOD

Under guidence of Dr neelam dogra ma’am

Presented by anuradha pandey

LEARNING OBJECTIVE

physiological changes which take place following birth and appreciate 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 irrespective of birth weightVERY LOW BIRTH WEIGHT(VLBW)<150O GRAMEXTREMELY LOW BIRTH WEIGHT(ELBW)< 1000 GRAM

INTRODUCTION

FETAL CIRCULATION

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)

FETAL CIRCULATION

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 foramenovale 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.

FETAL CIRCULATION (PARALLEL CIRCULATION)

PHYSIOLOGICAL CHANGES AT BIRTH

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 circulation

increase SVR

Reduction of blood flow along ductus venosus (passive closure over the following 3-7 days),reduced blood flow in IVC

Lung expansion

drops 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 fetal to postnatal circulation requires

clamping of umbilical cord and removal of the placenta

increased pulmonary blood flow,

Shunt closure

TRANSITION AT BIRTH

RESPIRATORY CHANGES

Chemical

Sensory/ Thermal

Mechanical InitiationInitiation ofof BreathingBreathing

What part do each of these factors play in initiation of

respirations in the neonate?

CHANGES AT BIRTH….MECHANICAL

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 (LaPlace’s relationships) 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

CHEMICAL EVENTS

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

SENSORY / THERMAL EVENTS 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

BIOPHYSICAL CHANGE CONTINUED

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

.

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- 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 Functional closure occurs by 60 hours in 93% of term infants.,4-

8 weeks permanent structural closure occurs via endothelial destruction and subintimal proliferation.

SHUNT CLOSURE

CARDIOVASCULAR CHANGES

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

SHUNT CLOSURE

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 transtubular system -nt

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.3 month parasympathetic vervous system effect more developed than sympathetivBaroreceptors not well developed compared to chemoreceptorsfurther depressed under anaesthesia-bradycardia

NEONATAL MYOCARDIAL FUNCTION

Ventricular maturation and associated ECG changes

The 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

LOW CARDIAC RESERVE-

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

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

MYOCARDIAL METABOLISM

neonates can tolerate hypoxia better due to

High concentration of glycogen

More effective utilisation of anaerobic metabolism

Hence can be resusitated easily if oxygenation and perfusion are reestablished

Oxygen consumption increases after birth(at neutral temperature )

Full term child

At birth-6ml/kg/min

10 days-7 ml/kg/min

4 week-8 ml/kg/min

CARDIAC VALUES

FETAL RESPIRATORY SYSTEM

ALVEOLAR DEVELOPMENTContinues even after birthAt birth 24 million alveoliincreases fivefold in -300 million by 8 years of ageInitally 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

FETAL RESPIRATORY SYSTEM

SURFACTANT type I and II pneumocytes are distinguishable only by 20-22 weeks

present only after 24 weeks, the watershed time for pulmonary gas exchange and therefore extra-uterine survivalproduction 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

.

RESPIRATORY SYSTEM

Diaphragm-two types of fibres

Type 1-slow twitch, highly oxidative ,sustained contraction ,less fatigue

Type 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

NEONATAL AIRWAY

NEONATAL AIRWAY

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

Large occiput-more flexion may lead to obstruction

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

DEVELOPMENTAL CHANGES OF RIB CAGE

NEONATAL LUNG MECHANICS

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 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

.

RESPONSE TO HYPOXIA

PERSISTENT PULMONARY HYPERTENSION OF THE NEW BORN/PERSISTENT FETAL CIRCULATION

PATHOPHYSIOLOGY

hypoxia, acidosis and inflammatory mediators l/t persistent increase in pulmonary artery pressure

persistent fetal circulation

Ppt condition-birth asphyxia,meconium aspiration sepsis,CDH, maternal use of nsaids,GDM,,casearen delivery

Leads to R TO L shunt resulting in profound hypoxia,with elevated PCO2

PERSISTENT FETAL CIRCULATION

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

MECONIUM ASPIRATION

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

GUIDELINES FOR MANAGEMENT FOR MECONIUM ASPIRATION

“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.”

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 Items on Bed

C old Walls

C old R oom T emp.

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 bodyweight (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 temperataure

2. Transmit impulses to the central nervous system

3. Which stimulates the sympathetic nervous system

4. Norepinephrine is released at local nerve endings in the brown

5. Metabolism of brown fat

6. Release of fatty acids

7. 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

HEAT CONSERVATION

Haematology

contains both adult (HbA) and fetal haemoglobin

HbF70-80% 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,

HAEMATOPOIESIS

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 INFANCY

Occcurs around 8-10 week of age

HbF is lost faster than HbA is synthesized.

low levels of erythropoietin due to improved tissue oxygenation after birth

decreased 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# immaturehepatocyte 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 thenewborn

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. 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.

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)

important postnatal adaptation to facilitate lung function and reduces the risks of symptomatic patent ductus arteriosus, necrotizing enterocolitis and bronchopulmonary dysplasia

BODY FLUID COMPOSITION

FLUID THERAPY

MAINTAINENCE FLUID-

70,80,90,120 ml/kg on day 1/3/5/7

Rest period-150ml/kg/24hr

Fluid choice

FIRST 48 hrs-10% glucose

Higher in pre term

Na and k 2-3 meq/100 ml

Beyond that-5% glucose(preterm higher glucose requirement)

IMPORTANT-newborn of diabetic mother, small for gestational age, glucose monitoring must

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(

NERVOUS SYSTEM

NERVOUS SYSTEM

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

NOCICEPTION

IMMUNOLOGIC ADAPTATION

Active acquired immunity Pregnant woman forms antibodies herself

Passive acquired immunity Mom passes antibodies to the fetus Lasts for 4-8 months

Newborn begins to produce own immunity about 4 weeks of age

KEY POINTS

KEY POINTS

THANK YOU