Infant respiratory distress syndrome
Encyclopedia
Infant respiratory distress syndrome (IRDS), also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome
in premature
infant
s caused by developmental insufficiency of surfactant
production and structural immaturity in the lung
s. It can also result from a genetic problem with the production of surfactant associated proteins. IRDS affects about 1% of newborn infants and is the leading cause of death in preterm
infants. The incidence decreases with advancing gestational age
, from about 50% in babies born at 26–28 weeks, to about 25% at 30–31 weeks. The syndrome is more frequent in infants of diabetic mothers and in the second born of premature twins.
IRDS is distinct from pulmonary hypoplasia
, another leading cause of neonatal death that involves respiratory distress.
, tachycardia
, chest wall retractions (recession), expiratory grunting, nasal flaring and cyanosis
during breathing efforts.
As the disease progresses, the baby may develop ventilatory failure (rising carbon dioxide concentrations in the blood), and prolonged cessations of breathing ("apnea
"). Whether treated or not, the clinical course for the acute disease lasts about 2 to 3 days. During the first, the patient worsens and requires more support. During the second the baby may be remarkably stable on adequate support and resolution is noted during the third day, heralded by a prompt diuresis. Despite huge advances in care, RDS remains the most common single cause of death in the first month of life of the developed world. Complications include metabolic disorders (acidosis, low blood sugar
), patent ductus arteriosus
, low blood pressure
, chronic lung changes, and intracranial hemorrhage
. The disease is frequently complicated by prematurity and its additional defects in other organ function.
seen in babies who die from RDS was the source of the name "hyaline membrane disease". These waxy-appearing layers line the collapsed alveoli of the lung. In addition, the lungs show bleeding, over-distention of airways and damage to the lining cells.
, which helps prevent collapse of the terminal air-spaces (the future site of alveolar
development) throughout the normal cycle of inhalation and exhalation. Surfactant is a complex system of lipid
s, protein
s and glycoprotein
s which are produced in specialized lung cells called Type II cells or Type II pneumocyte
s. The surfactant is packaged by the cell in structures called lamellar bodies
, and extruded into the air-spaces. The lamellar bodies then unfold into a complex lining of the air-space. This layer reduces the surface tension of the fluid that lines the air-space. Surface tension is responsible for approximately 2/3 of the elastic recoil forces. In the same way that a bubble will contract to give the smallest surface area for a given volume, so the air/water interface means that the liquid surface will tend towards being as small as possible, thereby causing the air-space to contract. By reducing surface tension, surfactant prevents the air-spaces from completely collapsing on exhalation. In addition, the decreased surface tension allows re-opening of the air-space with a lower amount of force. Therefore, without adequate amounts of surfactant, the air-spaces collapse and are very difficult to expand. Microscopically, a surfactant deficient lung is characterized by collapsed air-spaces alternating with hyper-expanded areas, vascular congestion and, in time, hyaline
membranes. Hyaline membranes are composed of fibrin
, cellular debris, red blood cell
s, rare neutrophils and macrophage
s. They appear as an eosinophilic, amorphous material, lining or filling the air spaces and blocking gas exchange. As a result, blood passing through the lungs is unable to pick up oxygen and unload carbon dioxide. Blood oxygen levels fall and carbon dioxide rises, resulting in rising blood acid levels and hypoxia
. Structural immaturity, as manifest by decreased number of gas-exchange units and thicker walls, also contributes to the disease process. Therapeutic oxygen and positive-pressure ventilation, while potentially life-saving, can also damage the lung. The diagnosis is made by the clinical picture and the chest xray, which demonstrates decreased lung volumes
(bell-shaped chest), absence of the thymus (after about 6 hours), a small (0.5–1 mm), discrete, uniform infiltrate (sometimes described as a "ground glass" appearance) that involves all lobes of the lung, and air-bronchograms (i.e. the infiltrate will outline the larger airways passages which remain air-filled). In severe cases, this becomes exaggerated until the cardiac borders become inapparent (a 'white-out' appearance).
("L/S ratio"), the presence of phosphatidylglycerol
(PG), and more recently, the surfactant/albumin (S/A) ratio
. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio <35 indicates immature lungs, between 35-55 is indeterminate, and >55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).
("CPAP"), and intravenous fluids are administered to stabilize the blood sugar, blood salts, and blood pressure. If the baby's condition worsens, an endotracheal tube (breathing tube) is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of surfactant
, either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs. One of the most commonly used surfactants is Survanta, derived from cow lungs, which can decrease the risk of death in hospitalized very-low-birth-weight
infants by 30%. Such small premature infants may remain ventilated for months. A line of research shows that an aerosol of perfluorocarbon can reduce inflammation in piglets. Chronic lung disease including bronchopulmonary dysplasia
are common in severe RDS. The etiology of BPD is problematic and may be due to oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks gestation is less than 10%.
Extracorporeal membrane oxygenation
(ECMO) is a potential treatment, providing oxygenation through an apparatus that imitates the gas exchange
process of the lungs. However, newborns cannot be placed on ECMO if they are under 4.5 pounds (2 kg), because they have extremely small vessels for cannulation, thus hindering adequate flow because of limitations from cannula size and subsequent higher resistance to blood flow (compare with vascular resistance
). Furthermore, in infants aged less than 34 weeks of gestation several physiologic systems are not well-developed, specially the cerebral vasculature and germinal matrix
, resulting in high sensitivity to slight changes in pH
, PaO2, and intracranial pressure. Subsequently, preterm infants are at unacceptably high risk for intraventricular hemorrhage
(IVH) if administered ECMO at a gestational age less than 32 weeks. Also later, given the risk of IVH, it has become standard practice to ultrasound the brain prior to administering ECMO.
Therefore, the device cannot be used for most premature newborns.
(ARDS) has some similarities to IRDS.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
in premature
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...
infant
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
s caused by developmental insufficiency of surfactant
Pulmonary surfactant
Pulmonary surfactant is a surface-active lipoprotein complex formed by type II alveolar cells. The proteins and lipids that surfactant comprises have both a hydrophilic region and a hydrophobic region...
production and structural immaturity in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s. It can also result from a genetic problem with the production of surfactant associated proteins. IRDS affects about 1% of newborn infants and is the leading cause of death in preterm
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...
infants. The incidence decreases with advancing gestational age
Gestational age
Gestational age relates to the age of an embryo or fetus . There is some ambiguity in how it is defined:*In embryology, gestational age is the time elapsed since conception. This interval is also termed fertilisation age....
, from about 50% in babies born at 26–28 weeks, to about 25% at 30–31 weeks. The syndrome is more frequent in infants of diabetic mothers and in the second born of premature twins.
IRDS is distinct from pulmonary hypoplasia
Pulmonary hypoplasia
Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that interfere with normal development of the lungs...
, another leading cause of neonatal death that involves respiratory distress.
Clinical course
IRDS begins shortly after birth and is manifest by tachypneaTachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...
, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, chest wall retractions (recession), expiratory grunting, nasal flaring and cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...
during breathing efforts.
As the disease progresses, the baby may develop ventilatory failure (rising carbon dioxide concentrations in the blood), and prolonged cessations of breathing ("apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
"). Whether treated or not, the clinical course for the acute disease lasts about 2 to 3 days. During the first, the patient worsens and requires more support. During the second the baby may be remarkably stable on adequate support and resolution is noted during the third day, heralded by a prompt diuresis. Despite huge advances in care, RDS remains the most common single cause of death in the first month of life of the developed world. Complications include metabolic disorders (acidosis, low blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
), patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
, low blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, chronic lung changes, and intracranial hemorrhage
Intracranial hemorrhage
An intracranial hemorrhage is a hemorrhage, or bleeding, within the skull.-Causes:Intracranial bleeding occurs when a blood vessel within the skull is ruptured or leaks. It can result from physical trauma or nontraumatic causes such as a ruptured aneurysm...
. The disease is frequently complicated by prematurity and its additional defects in other organ function.
Histopathology
The characteristic histopathologyHistopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
seen in babies who die from RDS was the source of the name "hyaline membrane disease". These waxy-appearing layers line the collapsed alveoli of the lung. In addition, the lungs show bleeding, over-distention of airways and damage to the lining cells.
Pathophysiology
The lungs of infants with respiratory distress syndrome are developmentally deficient in a material called surfactantPulmonary surfactant
Pulmonary surfactant is a surface-active lipoprotein complex formed by type II alveolar cells. The proteins and lipids that surfactant comprises have both a hydrophilic region and a hydrophobic region...
, which helps prevent collapse of the terminal air-spaces (the future site of alveolar
Pulmonary alveolus
An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...
development) throughout the normal cycle of inhalation and exhalation. Surfactant is a complex system of lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s which are produced in specialized lung cells called Type II cells or Type II pneumocyte
Type II pneumocyte
Type II pneumocytes also called great alveolar cells or septal cells are granular and roughly cuboidal in shape. Type II pneumocytes are typically found at the alveolar-septal junction...
s. The surfactant is packaged by the cell in structures called lamellar bodies
Lamellar bodies
Lamellar granules are secretory organelles found in type II pneumocytes and keratinocytes. They are oblong structures, appearing about 300-400 nm in width and 100-150 nm in length in transmission electron microscopy images...
, and extruded into the air-spaces. The lamellar bodies then unfold into a complex lining of the air-space. This layer reduces the surface tension of the fluid that lines the air-space. Surface tension is responsible for approximately 2/3 of the elastic recoil forces. In the same way that a bubble will contract to give the smallest surface area for a given volume, so the air/water interface means that the liquid surface will tend towards being as small as possible, thereby causing the air-space to contract. By reducing surface tension, surfactant prevents the air-spaces from completely collapsing on exhalation. In addition, the decreased surface tension allows re-opening of the air-space with a lower amount of force. Therefore, without adequate amounts of surfactant, the air-spaces collapse and are very difficult to expand. Microscopically, a surfactant deficient lung is characterized by collapsed air-spaces alternating with hyper-expanded areas, vascular congestion and, in time, hyaline
Hyaline
The term hyaline denotes a substance with a glass-like appearance.-Histopathology:In histopathological medical usage, a hyaline substance appears glassy and pink after being stained with haematoxylin and eosin — usually it is an acellular, proteinaceous material...
membranes. Hyaline membranes are composed of fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
, cellular debris, red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s, rare neutrophils and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s. They appear as an eosinophilic, amorphous material, lining or filling the air spaces and blocking gas exchange. As a result, blood passing through the lungs is unable to pick up oxygen and unload carbon dioxide. Blood oxygen levels fall and carbon dioxide rises, resulting in rising blood acid levels and hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. Structural immaturity, as manifest by decreased number of gas-exchange units and thicker walls, also contributes to the disease process. Therapeutic oxygen and positive-pressure ventilation, while potentially life-saving, can also damage the lung. The diagnosis is made by the clinical picture and the chest xray, which demonstrates decreased lung volumes
Lung volumes
Lung volumes and lung capacities refer to the volume of air associated with different phases of the respiratory cycle. Lung volumes are directly measured...
(bell-shaped chest), absence of the thymus (after about 6 hours), a small (0.5–1 mm), discrete, uniform infiltrate (sometimes described as a "ground glass" appearance) that involves all lobes of the lung, and air-bronchograms (i.e. the infiltrate will outline the larger airways passages which remain air-filled). In severe cases, this becomes exaggerated until the cardiac borders become inapparent (a 'white-out' appearance).
Prevention
Most cases of infant respiratory distress syndrome can be ameliorated or prevented if mothers who are about to deliver prematurely can be given glucocorticoids, one group of hormones. This speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The American College of Obstetricians and Gynecologists (ACOG), Royal College of Medicine, and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34 weeks of gestation. In pregnancies of greater than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid, obtained by inserting a needle through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the lecithin-sphingomyelin ratioLecithin-sphingomyelin ratio
The lecithin-sphingomyelin ratio is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs. This is especially important for premature babies trying to expand their lungs after...
("L/S ratio"), the presence of phosphatidylglycerol
Phosphatidylglycerol
Phosphatidylglycerol is a glycerophospholipid found in pulmonary surfactant.The general structure of phosphatidylglycerol consists of a L-glycerol 3-phosphate backbone ester-bonded to either saturated or unsaturated fatty acids on carbons 1 and 2. The head group substituent glycerol is bonded...
(PG), and more recently, the surfactant/albumin (S/A) ratio
Surfactant-albumin ratio
The surfactant-albumin ratio is a test for assessing fetal lung maturity....
. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio <35 indicates immature lungs, between 35-55 is indeterminate, and >55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).
Treatment
Oxygen is given with a small amount of continuous positive airway pressureContinuous positive airway pressure
Positive airway pressure is a mode of respiratory ventilation used primarily in the treatment of sleep apnea, for which it was first developed. PAP ventilation is also commonly used for those who are critically ill in hospital with respiratory failure, and in newborn infants...
("CPAP"), and intravenous fluids are administered to stabilize the blood sugar, blood salts, and blood pressure. If the baby's condition worsens, an endotracheal tube (breathing tube) is inserted into the trachea and intermittent breaths are given by a mechanical device. An exogenous preparation of surfactant
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...
, either synthetic or extracted from animal lungs, is given through the breathing tube into the lungs. One of the most commonly used surfactants is Survanta, derived from cow lungs, which can decrease the risk of death in hospitalized very-low-birth-weight
Birth weight
Birth weight is the body weight of a baby at its birth.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking and intelligence.-Determinants:There are...
infants by 30%. Such small premature infants may remain ventilated for months. A line of research shows that an aerosol of perfluorocarbon can reduce inflammation in piglets. Chronic lung disease including bronchopulmonary dysplasia
Bronchopulmonary dysplasia
Bronchopulmonary dysplasia is a chronic lung disorder that is most common among children who were born prematurely, with low birthweights and who received prolonged mechanical ventilation to treat respiratory distress syndrome...
are common in severe RDS. The etiology of BPD is problematic and may be due to oxygen, overventilation or underventilation. The mortality rate for babies greater than 27 weeks gestation is less than 10%.
Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation
In intensive care medicine, extracorporeal membrane oxygenation is an extracorporeal technique of providing both cardiac and respiratory support oxygen to patients whose heart and lungs are so severely diseased or damaged that they can no longer serve their function...
(ECMO) is a potential treatment, providing oxygenation through an apparatus that imitates the gas exchange
Gas exchange
Gas exchange is a process in biology where gases contained in an organism and atmosphere transfer or exchange. In human gas-exchange, gases contained in the blood of human bodies exchange with gases contained in the atmosphere. Human gas-exchange occurs in the lungs...
process of the lungs. However, newborns cannot be placed on ECMO if they are under 4.5 pounds (2 kg), because they have extremely small vessels for cannulation, thus hindering adequate flow because of limitations from cannula size and subsequent higher resistance to blood flow (compare with vascular resistance
Vascular resistance
Vascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. The resistance offered by the peripheral circulation is known as the systemic vascular resistance , while the resistance offered by the vasculature of the lungs...
). Furthermore, in infants aged less than 34 weeks of gestation several physiologic systems are not well-developed, specially the cerebral vasculature and germinal matrix
Germinal matrix
In anatomy, the germinal matrix is a highly cellular and highly vascularized region in the brain from which cells migrate out during brain development. The germinal matrix is the source of both neurons and glial cells and is most active between 8 and 28 weeks gestation...
, resulting in high sensitivity to slight changes in pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, PaO2, and intracranial pressure. Subsequently, preterm infants are at unacceptably high risk for intraventricular hemorrhage
Intraventricular hemorrhage
An intraventricular hemorrhage , often abbreviated "IVH," is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space...
(IVH) if administered ECMO at a gestational age less than 32 weeks. Also later, given the risk of IVH, it has become standard practice to ultrasound the brain prior to administering ECMO.
Therefore, the device cannot be used for most premature newborns.
Related disorders
Acute respiratory distress syndromeAcute respiratory distress syndrome
Acute respiratory distress syndrome , also known as respiratory distress syndrome or adult respiratory distress syndrome is a serious reaction to various forms of injuries to the lung....
(ARDS) has some similarities to IRDS.
Famous victims
- In 1963, Patrick Bouvier Kennedy, son of President John F. KennedyJohn F. KennedyJohn Fitzgerald "Jack" Kennedy , often referred to by his initials JFK, was the 35th President of the United States, serving from 1961 until his assassination in 1963....
and First Lady Jacqueline Kennedy, died of RDS two days after his premature birth at 34 weeks gestation.
- In 1992, Freddie HighmoreFreddie HighmoreAlfred Thomas "Freddie" Highmore is an English actor. He is best known for his roles in the films Finding Neverland, Five Children and It, Charlie and the Chocolate Factory, Arthur and the Invisibles, August Rush, The Golden Compass, The Spiderwick Chronicles, and Toast.-Early life:Highmore was...
survived RDS after being born at 29 weeks gestation.
External links
- Hyaline membrane disease photos at: Atlas of Pathology
- Signs & Symptoms