Hyaline Membrane DiseaseVincent 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•15-20 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

16-33 days AOG

7-16th weeks AOG

16th-25th 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)

28-32 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 ProteinsHydrophobic

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 SynthesisNormal 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 weeks15-30% of infants 32-36 weeksRare in term neonates (consider genetic abnormalities in surfactant proteins)

Incidence increases with:Maternal DMMultiple gestationsAsphyxiaCold stressMaternal history of previously affected infants

Pathophysiology

Poor Surfactant Quantity and QualityLungs 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 exchangeResults 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 ProcessesLow surfactant

levels

Small Alveoli

Chest Compliance

ATELECTASIS HYPOXEMIA

HYPERCAPNIA

Pulmonary Artery Constriction

Pulmonary Artery

Constriction

Shunting

Alveolar Ventilation Impaired

Ischemic Injury to the

lungs

Proteinaceous effusion into the alveolar

space

Clinical ManifestationsHISTORY

Often preterm

Had asphyxia in the perinatal period

Respiratory distress at birth

Apnea

PHYSICAL EXAM

Tachypnea

Grunting

Nasal flaring

Retractions

Cyanosis

Decreased breath sounds

**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

DifferentialsDiagnosis Key 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 – 24-34 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 ReplacementConsidered the standard of care in RDS

Surfactant prophylaxis (within 15 minutes of birth) to all infants <27 weeks.

Consider prophylaxis if 27-29 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 <7.20 and PCO2 >60 mmHg)

Hypoxemia

Severe apnea

Unresponsive and limp babies with impending respiratory distress

Target Values

Oxygen SaturationSaturations above 95% and below 89% are associated with poor outcomesO2sat by Pulse ox – 90-95% is optimal

PCO2 levels45-60 mmHg is the optimal levelIf it exceeds 60 mmHg, the pH falls <7.25 which is associated with poor CV functionBabies initially on CPAP that develop acidosis, should be intubated

Sedation and Pain ReliefAdvantages

Improved ventilatory synchrony and pulmonary function

Neuroendocrine responses are alleviated

Decreased adverse long term neurologic sequelae

Disadvantages

Side effectsMorphine – hypotension

Fentanyl – rigid chest wall

Benzo’s – Tolerance and dependence

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.