Post on 14-Aug-2019
Respiratory Embryology and Common
Pathophysiology
Sharon Fichera RN, MSN, CNS, NNP-BC Newborn & Infant Critical Care Unit
Children’s Hospital Los Angeles
Embryonic development week 1 – 5 The foregut provides a single lung bud which begins to divide. At the same time the pulmonary vein develops and joins the lung bud. The Trachea is developed by the end of the embryonic period Trachea, L & R mainstem with beginning development of the lobes of the lung
End of the Embryonic Period
Embryonic lung development
1 – left main stem bronchus
11 – Right inferior bud
12 – Right middle bud
13 – Right superior bud
Pseudoglandular period 6 – 16 weeks Lung under goes 14 generations of branching and the formation of the terminal bronchioles
Canalicular period 16 – 24 weeks gas exchanging units beginning to form. Type II alveolar cells are present. Vascular system develops and is closer to the conducting airways
Terminal sac period 26 weeks – birth more budding and there is an exponential increase in surface area. Type II pneumocytes are producing surfactant
Biochemical Events Reduction of surface tension by the production of surfactant – prevents collapse of the alveoli at the end of expiration
Surfactant is produced by the type II pneumocytes at approximately 25 weeks.
It is the phospholipids that have the surface-active properties,
DPPC – Dipalmitoylphosphatidylcholine is the major phospholipid that reduces the surface tension
Surfactant Proteins Hydrophilic
Surfactant Protein A – most abundant, with B makes the tubular myelin lattice network Activates the alveolar macrophages – host defence
Surfactant Protein D – is upregulated during inflammation and may have a role in host defence
Hydrophobic
Surfactant B – important in making the tubular myelin lattice. Also enhances the update and recycling of surfactant
Surfactant C – Assists with the absorption and spreading of the surfactant. Also assists with surfactant recycling
Gestational Age Assessment &
Surfactant Fetal kidney makes most of the amniotic fluid, the fetal lung makes fluid independently of the kidney
Sphingomyelin - a phospholipid (fat) is produced in the Endoplasmic Reticulum (ER) within the cell. Level remains constant after 30 weeks.
Lecithin - a phospholipid that is in low concentrations until 30 weeks and increases with a peak at 36 weeks
Phosphatidylglycerol - a phospholipid that also peaks at 36 weeks
Phospholipids and usefulness in gestational age assessment
L/S ratio: The lecithin to sphingomyelin ratio to assess for lung maturation
>2:1 is considered mature
Presence of Phosphatidylglycerol - PG most reliable measurement for IDM
ACOG 2011 - Position on Corticosteroids
risk of delivery at 24-34 weeks
May not be beneficial if delivery is imminent
No contraindication if chorioamnionitis is present
Meerstadt, PWD., Gyll, C. Maanual of Neonatal Emergency X-Ray interpretation. 1994; London, W.B. Saunders.
Meerstadt, PWD., Gyll, C. Maanual of Neonatal Emergency X-Ray interpretation. 1994; London, W.B. Saunders
Meerstadt, PWD., Gyll, C. Maanual of Neonatal Emergency X-Ray interpretation. 1994; London, W.B. Saunders
RDS Respiratory Distress
Syndrome Surfactant deficiency Lung immaturity RDS/Pneumonia 48-72 hours - type II pneumocytes will make surfactant Treatment - Surfactant (1990's) Natural surfactants: Survanta -bovine Curosurf - porcine Infrasurf - calf lung Routine NICCU care
Treatment Approach Prophylaxis - In the DR, preferably prior to breathing (15 min)
Early rescue - Within 1-2 hours
Late rescue - within 4-12hours and progressive FiO2 requirement
Insure - Intubate - surfactant - extubate
Non-invasive administration
Outcomes for infants randomly assigned to continuous positive airway pressure (CPAP) initiated in the delivery room or intubation and surfactant treatment in the delivery room. The combined outcome of death or bronchopulmonary dysplasia significantly favored the CPAP group. Data from Schmölzer et al. (24)
Alan Jobe Neoreviews 2014; 15:e236-e245; doi:10.1542/neo.15-6-e236
Decrease in death from respiratory distress syndrome (RDS) from 1970 to 2010. Infant mortality has decreased by 95%, although the infants coded as having RDS have gotten smaller and more immature. The years for introduction of the interventions into clinical practice are indicated on the graph. Figure redrawn from data in Lee et al (49) with additional data for 2010 to 2011 from Hamilton et al. (50) CPAP=continuous positive airway pressure; PEEP=positive end-expiratory pressure. • Alan Jobe Neoreviews 2014; 15:e236-e245; doi:10.1542/neo.15-6-e236
Can We Prevent RDS? Maternal glucocorticoids/antenatal steroids
Elective C/Section a Neonatal Danger
Determine lung maturity
L/S ratio of at least 2:1
Presence of PG
Transient Tachypnea of the Newborn (TTN)
Retained Lung Fluid Syndrome Delayed clearance of lung fluid – who is at risk? A. Term, near term and post term – new terminology B. Elective C/Section without labor C. Prematurity, precipitous delivery
How does the lung fluid get removed?
TTN Maybe difficult to distinguish from other diseases:
Differential:
RDS
Pneumonia
Maybe a diagnosis of exclusion. Pt is usually term, and symptoms may be mild
Meerstadt, PWD., Gyll, C. Maanual of Neonatal Emergency X-Ray interpretation. 1994; London, W.B. Saunders
Pneumonia Congenital vs acquired
Risk is inversely related to gestational age
Maybe associated with chorioamnionitis, or maternal UTI
Prolonged rupture of membranes
Transplacental
RDS vs Pneumonia
RDS vs Pneumonia Suspicious
Suspicious
&
More Suspicious
Any baby with respiratory distress needs an evaluation for sepsis/pneumonia and treatment with antibiotics until infection is ruled out!
Meconium Aspiration MAS – 8-29% of all deliveries
Occurs in the near term, term and post dates babies
Aspiration occurs about 5%
Ball valve effect vs chemical pneumonitis
Hyperinflation, with areas of collapse
Chemical pneumonitis initiates an inflammatory response
Causing cytotoxic edema, washing out inactivating the surfactant
Meconium Aspiration Asphyxia, effects of chronic hypoxia may result in PPHN
Delivery room management
May have signs of prolonged placental insufficiency – cachectic
Barrel shaped chest
May benefit from surfactant (lessen airleaks)
Persistent Pulmonary Hypertension (PPHN) Fetal Circulation
Blood enters the umbilical vein from the placenta - goes through the Ductus Venosus into the IVC
Enters the right atrium crosses through the Foramen Ovale into the left Atrium
Blood (used by the body) coming back to the right Atrium, right Ventricle goes right to left through the Ductus Arteriosus into the Aorta
Lungs - high pressure
Body - low pressure
Newborn Circulation Normal Transition
Cord is clamped - placental separation SVR rises
Lungs fill with air and expand
Mechanical compression of pulmonary vessels is released and pulmonary blood flow increases PVR falls
Ductus Venosus - closes 3d-2 weeks
Ductus Arteriosus - closes 1 day - month
Foramen Ovale
When is PPHN diagnosed? Due to elevated
pulmonary vascular resistance
77% <24 hours
93% <48 hours
97% <72 hours
1.9 per 1000 births
Why do babies get PPHN? Heart/Lung/Pulmonary Vasculature
Lung *Meconium
Aspiration Syndrome
*Pneumonia
*Lung Hypoplasia
*RDS
Why do babies get PPHN? Heart/Lung/Pulmonary Vasculature
Pulmonary Vasculature Reactivity/underdevelopme
nt
Renal/pulmonary development
Congenital diaphragmatic hernia
CCAM’s
Sepsis - cytokine mediated response
Why do babies get PPHN? Heart/Lung/Pulmonary Vasculature
Heart Congenital Heart
Disease
Hypoxic ischemic injury
PPHN Vasodilators Vasoconstrictors
Hypoxia
Acidosis
Hypercarbia
Deficient prostacyclin
Deficient NO
Excessive thromboxane, leukotrienes, endothelin & platelet-activating factor
Oxygen
Alkalosis
Hypocarbia
Nitric Oxide
Phosphodiesterase inhibitors
Prostacyclin
Diagnosis of PPHN Cardiac ECHO
Pre & post ductal oxygen saturation
Complications Air leaks DIC
Systemic hypotension HIE
AKI (ARF, ATN)
Treatment Normalize blood gases
Oxygen/ventilation
iNO
Surfactant replacement?
Sedate
Maintain systemic blood pressure – inotropes
Antibiotics
Phosphodiesterase 3 inhibitor
Phosphodiesterase 5 inhibitor
(sildenafil)
ECMO
Mortality and need for ECMO vary by center and is somewhere between 20-40%
Long term morbidity is often hidden and may be seen in sensorineural hearing loss and abnormal neurologica outcomes
Bronchopulmonary Dysplasia Chronic Lung Disease
First described in 1967 by Northway
(2001) Jobe/Bancalari - <32 week who has been on O2>28 days by 36 weeks PCA is still requiring O2 or Ventilation
Introduction of surfactants has changed the presentation of classic BPD
Inflammatory mediators may play a role in BPD (chioamnionitis)
Acute lung injury, arrested development and abnormal repair processes
BPD Inflammatory mediators
Oxygen toxicity - ROS, Pulmonary edema
Assisted Ventilation/PPV – Barotrauma, volutrauma
L R shunting via a PDA
Inverse relationship to gestational age
Nutrition
Prevention & Management Prevention
Prevent preterm birth
Antenatal corticosteriods ?
Gentle ventilation/permissive hypercapnia and early extubation
HFOV?
Steriods - AAP does not recommend (2010)
Management
Minimize length of intubation/IMV
nCPAP/NIPPV
SIMV/NAVA
Oxygen targeting
OWL
Oxygen swings
Management Diuretics ?
Caffeine – lung protective, reduces length of time on the ventilator
Nutrition – 150-180 kcal/kg
Steroids ? Inhaled steroids?
Morbidities -
neurodevelopmental, hearing loss, vision, cerebral palsy
Apnea Periodic Breathing
An irregular pattern with 5-10 second pauses, followed by rapid breahing
30-90% of preterm infants, disappears near term
No changes in HR or color
Apnea
20 second pauses
Shorter if HR or color change occurs
Most apnea occurs in healthy premies
<1000gms – 80% will have apnea
Apnea Types Primary apnea – will respond to stimulation and resume breathing
Secondary apnea – requires PPV to establish breathing for each minute of PPV the baby has been in secondary apnea for 2 minutes
Central apnea – no air flow (15% of all apneas)
Obstructive apnea – may appear to be breathing, but with no air flow (30% of apneas)
Mixed apnea – combination of central and obstructive (50-60%)
Idiopathic apnea – diagnosis of exclusion, found in otherwise healthy preterm infants
Evaluation & Treatment R/O airway anomalies
If new onset >than 48 hrs – sepsis evaluation and ECHO
R/O seizures
Methylxanthines – aminophylline, caffeine
Doxapram
References Verklan, T., Walden, M. Core curriculum for neonatal intensive care nursing (5th Ed.) 2010, St. Louis, Elvsevier Saunders, pp.447-511.
Meerstadt, PWD., Gyll, C. Maanual of Neonatal Emergency X-Ray interpretation. 1994; London, W.B. Saunders
England, M. A color atlas of life before birth: normal fetal development 1990. Chicago, Ill. Year Book Medical Publishers.
Moore, k., Persaud, T., The developing human: Clinically oriented embryology 1993. St. Louis, W.B.Saunders.
Jobe, A. Surfactant: The basis for clinical treatment strategies. In Polin, R., Banacalari, E.’s The newborn lung: Neonatology questions and controversies. 2008. St. Louis, Elvsevier Saunders, pp.73-101.