Hyaline Membrane Disease Vincent Patrick Uy

Infant’s First Breath Intermittent compression of the thorax facilitates removal of lung fluids Surfactant DECREASES surface tension to allow low pressure to aerate the lungs – preventing alveolar collapse Functional residual capacity (FRC) must be established Air entry into the alveoli displaces fluid, decreases the hydrostatic pressure and increase pulmonary blood flow.

Infant’s First Birth Decline in PaO2 Decline in pH Rise in PaCO2 Redistribution of the cardiac output Decrease body temperature Tactile and sensory inputs

Timeline of Lung Development Embryonic Period Protrusion from the foregut Initial branching Pseudoglandular generations of air branching Progressive epithelial differentiation Canalicular Bronchioles and ducts of gas exchange regions are formed Alveolar Type II cells Saccular Stage Gas exchange may be possible Septal growth into saccules and into alveoli days AOG 7-16 th weeks AOG 16 th -25 th week AOG >24 weeks AOG

Lung Surfactant Type II pneumocytes Reduces surface tension allowing lesser pressures to maintain the alveoli open.

Lung Surfactant 20 weeks – start to appear (appearance of lamellar bodies) weeks – detectable in amniotic fluid 35 weeks – “Mature” levels of surfactant

Components of Lung Surfactant Lipids (70%) Majority of the lipid component is dipalmitoylphosphatidyl choline (DPPC) which is the major surface tension reducing substance Proteins (30%) Hydrophobic surfactant proteins (SP) B & C Hydrophilic SP A & D

Surfactant Proteins Hydrophobic SP – B Surface tension lowering capabilities Homozygous deficiency is lethal in term infants. Found in commercially prepared surfactant with SP-C SP – C Surface tension lowering capabilities Deficiency results in interstitial lung disease Works cooperatively with SP-B by spreading the phospholipids over the alveolar surface Hydrophilic SP – A Innate host defense protein Phagocytosis SP-A increase with steroid exposure Not found in commercially prepared surfactant SP – D Innate host defense mechanisms Has limited roles in humans

Lung Surfactant

Synthesis, Secretion and Adsorption of Surfactant Tubular Myelin Type II pneumocyte Lamellar body

Law of Laplace

Factors that Enhance Surfactant Synthesis Normal pH Normal temperature of the neonate Normal perfusion Adequate amount of oxygen Low insulin levels Chronic intrauterine stress (Pregnancy-induced hypertension) Twin gestations Antenatal corticosteroids

Hyaline Membrane Disease Occurs primarily in premature babies; inversely related to gestational age 60-80% of infants <28 weeks 15-30% of infants weeks Rare in term neonates (consider genetic abnormalities in surfactant proteins) Incidence increases with: Maternal DM Multiple gestations Asphyxia Cold stress Maternal history of previously affected infants

Pathophysiology Poor Surfactant Quantity and Quality Lungs of premature babies have surfactant rich in phosphatidylinositol and smaller amounts of phosphatidylglycerol (PPG). PPG has the greatest surface activity. Protein content of surfactant from preterm lung is low relative to the amount of phospholipids. Inflammation and pulmonary edema ensues

Pulmonary Edema Leads to poor gas exchange Results from inflammation and lung injury Reduced pulmonary fluid reabsorption Low urine output Proteinaceous edema and inflammatory cytokines increase the conversion rate of surfactant into inactive forms.

Lung Mechanics in Preterms Worsening RDS with formation of hyaline membranes result in less compliant lungs Lower part of the chest is pulled in as the diaphragm descends  intrathoracic pressure is more negative  atelectasis Highly compliant chest wall  less resistant  volume of the lung tends to approach RV  Atelectasis

Disease Processes Low surfactant levels Small Alveoli  Chest Compliance ATELECTASIS HYPOXEMIA HYPERCAPNIA Pulmonary Artery Constriction Shunting Alveolar Ventilation Impaired Ischemic Injury to the lungs Proteinaceous effusion into the alveolar space

Clinical Manifestations HISTORY Often preterm Had asphyxia in the perinatal period Respiratory distress at birth Apnea PHYSICAL EXAM **Classic chest radiograph is also an additional feature of the disease.

Diagnostic Tests Chest Radiograph Blood Gas sampling Sepsis Work-up Serum glucose levels Serum electrolytes and calcium levels Echocardiography

Differentials DiagnosisKey Points Transient Tachypnea of the NB Mature infants Milder respiratory distress with quick improvement Rarely will require mechanical ventilation Bacterial Pneumonia and Sepsis Signs and symptoms overlap with RDS Infants with respiratory distress will need blood cultures Air Leak Syndromes May result from RDS and treatment of RDS Congenital Heart Disease If lung function does not improve after support and surfactant therapy, obtain an ECHO.

Preventive Management Avoid unecessary and untimely Cesarean sections. Antenatal Corticosteroids – weeks gestation – is associated with overall reduction in neonatal deaths, RDS, IVH, NEC, ICU admissions and systemic infections in the first 48 hours of life Betamethasone: Two 12 mg doses IM given 24 hours apart Dexamethasone is no longer given due to increase risk of cystic periventricular leukomalacia among preemies

Surfactant Replacement Considered the standard of care in RDS Surfactant prophylaxis (within 15 minutes of birth) to all infants <27 weeks. Consider prophylaxis if weeks if baby was intubated or mother did not get antenatal steroids Repeated doses every 6-12 hours for a total of 3-4 doses.

Natural Surfactant Obtained from animal lung lavage or by mincing lung tissues Lipid extraction removes hydrophilic components (SP- A and SP-D). The purified lipid derivative contains the necessary components to control the surface tension Choice of natural surfactant is based on clinician/hospital preference

Respiratory Management Because of increase risk of BPD, preterm infants without signs of respiratory failure can be managed with CPAP or NIPPV

Respiratory Management Indications for immediate intubation and mechanical ventilation: Respiratory acidosis (pH 60 mmHg) Hypoxemia Severe apnea Unresponsive and limp babies with impending respiratory distress

Target Values Oxygen Saturation Saturations above 95% and below 89% are associated with poor outcomes O2sat by Pulse ox – 90-95% is optimal PCO2 levels mmHg is the optimal level If it exceeds 60 mmHg, the pH falls <7.25 which is associated with poor CV function Babies initially on CPAP that develop acidosis, should be intubated

Sedation and Pain Relief Advantages Improved ventilatory synchrony and pulmonary function Neuroendocrine responses are alleviated Decreased adverse long term neurologic sequelae Disadvantages

Supportive Measures Umbilical artery line Thermoregulation Fluid management Treat hypotension with vasopressor support and cautious use of saline boluses Early nutrition

Complications Survival from HMD is dependent of gestational age and birthweight Major morbidities such as IVH, BPD and NEC remain high in smaller infants Endotracheal tube complications Air leak syndromes – rupture of overdistended alveoli BPD

Bronchopulmonary Dysplasia Result of lung injury among infants managed with mechanical ventilation and supplemental oxygen Defined as persistent oxygen dependency up to the 28 day of life.