RDS Flashcards
Etiology of Respiratory Distress
Respiratory Distress Syndrome (surfactant def.) Airleak Meconium Aspiration Syndrome Neonatal Pneumonia Pulmonary Hemorrhage Transient tachypnea
RDS is caused by ..
Usually seen in who ..
Leads to …
Caused by deficiency of surface-active material (surfactant) at the alveolar air-liquid interface
Usually in premature babies
Leads to poorly compliant lungs, atelectasis, an increased work of breathing, and hypoxia
At 29 weeks gestational age, what % will have RDS?
60%
Basic pathways for surfactant metabolism
Surfactant is synthesized in type II cells, stored in lamellar bodies, and secreted into the alveoli where it forms a surface film.
It is cleared from the airspaces by macrophages for catabolism or is taken back into type II cells where it is reprocessed and resecreted, a recycling pathway.
Risk factors for RDS
IDM, fetal hyperinsulinism impedes surfactant production Fetal asphyxia Multiple gestation Males>females Caucasian>African-Americans
What are the 5 main phases of embryonic lung development?
Which phases are important for conducting airways? terminal respiratory units?
Embryonic Pseudoglandular Canalicular Terminal Sac Alveolar
1,2 - conducting airways
3,4,5 - terminal respiratory units
Embryonic Period of Lung Development
0 - 6 weeks gestation
proximal airways: bronchi
Glandular Period of Lung Development
7 - 16 weeks
- -conducting airways: terminal bronchioles
- -branching pattern: represents permanent branching pattern
Canalicular Period of Lung Development
17 - 25 weeks
- -acini, gas exchange unit of lung associated with single terminal bronchiole
- -Respiratory Bronchiole, Alveolar Duct & Sac
- -full complement of 25,000 terminal bronchioles should be present by 27 weeks
- -Type II alveolar cells present at 20 weeks
What do Type II alveolar cells do?
Produce surfactant
What do Type I alveolar cells do?
Gas exchange
Terminal Sac period/Subsaccular phase of lung development
25 -35 weeks
primitive alveoli, subsaccules, appear
- -decrease thickness of interstitium, thinning of epithelium & beginning of septation of terminal air units
- -increase in alveoli, lung volume & surface area indicate the anatomic potential for gas exchange
- -Type I & Type II cells differentiate
- –enlargement of gas exchange surface
- -lamellar bodies develop, increase in size & number
- –increase storage of surfactant lipids
- -Exponential increase in lung volume and surface area as the primitive alveoli appear
Alveolar period of lung development
36 weeks - 3 years old
- -50 million alveoli at term; 300 million at 3 years
- -Area increase from 3-4 m2 to 75-100m2 by adult
- -invagination of terminal saccules & formation of secondary protrusions
- -protrusions elongate & thin forming alveoli
- –volume of potential air space increases
- –continued differentiation of Type II cells
- -collagen synthesis -provides strength
- -elastin accumulation - provides distensibility
- -Further thinning of interstitium
- -appearance of a single capillary network in which one capillary bulges into the lumen of both alveoli with which it is affiliated
What is surfactant composed of?
Saturated phosphatidylcholine (50%) Unsaturated phosphatidylcholine (20%) Neutral lipids (8%) Phosphatidylglycerol Other phospholipids Surfactant proteins
Most tests today are based on PC which appears at 28 weeks of gestation
Surfactant Synthesis
- -Surfactant phospholipids synthesized in smooth e.r. of Type II Alveolar Cells (10% of lung surface area)
- -packaged by Golgi apparatus; stored as Lamellar Bodies
- -secreted by exocytosis
- -converted to tubular myelin
- -rapid provision of phospholipid monolayer to surface interface
Surfactant Proteins: SP-A, SP-B, SP-C, SP-D
–what is their role?
- -Enhance the spreading and stability of phospholipid films.
- -Determine the structure of surfactant in lamellar bodies and tubular myelin.
- -Regulate surfactant phospholipid homeostasis.
- -Regulate innate host defense.
What substances are helpful/important in surfactant development?
Corticosteroid and thyroid hormones have a regulatory role
Circulating catecholamines stimulate surfactant secretion during labor and birth
Lung distention after birth stimulates surfactant secretion
SP-A deficiency
Forms integral part of tubular myelin (SP-B required)
Inhibits surfactant secretion but stimulates reutilization
May have a role in determining surfactant pool size
Host defense – opsonization, viral pathogen protection
SP-A Null Mice: Lung inflammation, no tubular myelin
SP-D deficiency
Innate host defense - viral
Surfactant lipid homeostasis
Protection from oxidant injury
SP-D Null Mice: Altered surfactant homeostais-( pool size) & Viral infections
SP-B deficiency
MOST IMPORTANT PROTEIN IN SURFACTANT
Surface tension reduction (Accelerate adsorption of phospholipid to air-fluid interface)
Formation of mature lamellar bodies
Formation of Tubular myelin
SP- A needed and enhances ability to reduce surface tension
Genetic defect – Alveolar proteinosis
SP-C deficiency
Surface adsorption of phospholipids
SP-C Null Mice: minimal effect
What agents inhibit surfactant function?
Albumin Amniotic Fluid Bilirubin Cholesterol Elastin Fibrin Monomers Fibrinogen Hemoglobin Immunoglobulins Meconium Plasma/serum RBC membrane
Laplace’s Law
P = 2T / r
- -models a single alveoli as a perfect sphere
- -Pressure required to keep alveoli distended is directly proportional to surface tension (T) and inversely proportional to the alveolar radius ( r )
How does surfactant work?
Aggregate at surface of alveolar lining liquid
REDUCE SURFACE TENSION by displacing water molecules
Surfactant lowers surface tension to near zero (as more water is displaced from the monolayer) and allows for the smallest of alveoli to remain distended at full lung deflation
THUS: surface area is maximized for gas exchange throughout the respiratory cycle
RDS pathogenesis regarding surfactant
- -deficient surfactant at air-fluid interface of alveoli in immature lungs
- -problem with secretion not with synthesis
- -Deficiency leads to areas of atelectasis
- -Other alveoli over distend (when on ventilator) and epithelial damage occurs & proteins leak into the airspace further impairing surfactant function
- –the protein that leaks is what gives the hyaline membrane
Summarize the problems that result from RDS
poor alveolar stability right-to-left shunting of blood reduced effective pulmonary blood flow pulmonary edema hyaline membrane development reduced lung compliance
Clinical manifestations of RDS
- -premature infants
- -tachypnea, central cyanosis, labored breathing: retractions, flaring and grunting
- -auscultation may reveal fine rales
What does grunting do?
Grunting is caused by partial closure of the glottis during exhalation to prevent alveolar collapse
–this increases the pressure
Laboratory findings with RDS
Laboratory: hypoxia, hypercarbia, acidosis
Radiographic findings with RDS
Radiographic
granular densities appear within hours of birth
‘ground glass’ appearance
RDS prevention
Reduce premature births
Predict pregnancies at risk ( 24-34 weeks gestation, intact membranes and impending delivery) and treat with antenatal glucocorticord hormones
Prophylactic/Early treatment of high risk infants (<30 weeks gestation) with exogenous surfactant in delivery room
RDS Treatment
Resuscitation by skilled team
Intratracheal administration of exogenous surfactant
Meticulous neonatal care (thermal neutrality, infection control, nutrition, fluids)
Assisted ventilation
Prognosis of RDS
Survival is directly related to birth weight and gestational age, and is affected by the above measures of prevention and treatment.
Long term prognosis for most is excellent: 85-90% are normal.
