Complications of Development
And Congenital Disease
Problems associated with premature
birth
Neonatal respiratory distress
syndrome (NRDS), otherwise known
as hyaline membrane disease, occurs in approximately 2% of all births and is
characterized by rapid, laboured breathing and often sternal retraction due to
partial collapse of the lungs after each breath. Lung compliance is low. NRDS
is most commonly caused by lack of sufficient quantities of surfactant and
consequent high surface tension in the alveoli and small airways. Incidence
therefore increases sharply with the degree of prematurity (Fig. 17a), although
other factors may also reduce production of surfactant. When a premature birth
is anticipated, the expectant mother can be treated with corticosteroids (betamethasone)
to speed fetal lung development and surfactant production. Treatment with exogenous
surfactant in the first 30 minutes after birth, either of natural origin or
artificial has also proved to be beneficial Survival of neonates with NRDS
often requires high positive-pressure mechanical ventilation and high levels of
oxygen.
The large majority of NRDS cases are
related to prematurity, with some due to other causes including damage to type
II pneumocytes. A very few cases are due to a congenital absence of pulmonary
surfactant protein B. These patients do not respond to any form of
therapy and tend to die in the f rst few months of life.
Bronchopulmonary dysplasia (chronic lung disease of the new born) is a long term
consequence of NRDS, primarily as a result of treatment with high
positive-pressure ventilation combined with high levels of oxygen (hyperoxia).
The condition is characterized by alterations in the structure and function of
airways and pulmonary blood vessels, including increases in airway and vascular
smooth muscle and obliteration of some microstructures. This leads to poorly
reversible airway obstruction and sometimes pulmonary hypertension (high pulmonary
blood pressure). Survivors may retain symptoms for many years, if not for life.
There are several similarities to chronic obstructive pulmonary disease (COPD,
Chapter 26) and chronic severe asthma in adults.
Several techniques have recently been
designed to minimize the incidence of bronchopulmonary dysplasia in infants
with NRDS. These include extracorporeal membrane oxygenation (ECMO),
where blood is circulated via external apparatus for gas exchange; mechanical ventilation
and hyperoxia are therefore not required and some success has been reported.
Conversely, ECMO has not been found useful in adults with acute respiratory
distress syndrome (ARDS, Chapter 41). Partial fluid ventilation, where
the lungs are ventilated with fluid containing oxygen-carrying perfluorocarbons
has also been reported to be beneficial Fluid ventilation circumvents problems
associated with high surface tension by removing the air-liquid interface and
allows small airways to open and contribute to gas exchange.
Congenital diseases
Congenital diaphragmatic hernia is the most common cause of lung hypoplasia
(inadequate development of the lung), with an incidence
of about one in 2000 births. Failure
of the diaphragm to fuse with the membranes on the thoracic and peritoneal wall
leads to a posterolateral defect, most commonly occurring on the left side (
85%), through which the abdominal viscera pass (herniate) into the thorax (Fig.
17b). This often includes the stomach, spleen and much of the intestines. The
presence of the resultant mass severely restricts lung development and later
inflation leading to a significantly reduced lung volume and life-threatening
breathing difficulties. The latter are the prime cause of death in congenital
diaphragmatic hernia, and most infants will die because the lungs are
insufficiently developed to support life outside the uterus. Although surgical
correction of the defect is possible both before and after birth, the mortality
rate is very high. A related but very much less common condition is eventration
of the diaphragm, where half the diaphragm lacks adequate muscle and bulges
(eventrates) into the thoracic cavity. The viscera are forced into the pocket
so formed, again restricting lung development.
Tracheo-oesophageal fistula (an opening between oesophagus and trachea) is the
most common abnormality of the lower respiratory tract itself, with an
incidence of about one in 4000 births. Its origins are located in the fourth
week of development, when the embryonic respiratory tract starts to develop
and divide from the embryonic oesophagus (Chapter 16). Eighty-five percent of
cases are associated with the descending part of the oesophagus having a
blind ending (oesophageal atresia) (Fig. 17c); the lower part of the
oesophagus joins instead to the base of the trachea. As a result, normal
feeding is impossible and the gut becomes distended with air. There are also
consequences in utero, as normally amniotic flui is ingested by the fetus.
Thus, oesophageal atresia is commonly associated with excess amniotic fluid (polyhydramnios),
which can lead to severe defects in the central nervous system. Some 5% of
cases of tracheo-oesophageal fistul show no atresia but only a fistula and
the remainder less common variations. Rare defects involving blockage or
narrowing of the trachea itself (tracheal atresia/stenosis) are nearly
always accompanied by various types of tracheo-oesophageal fistula
There are many inherited disorders
of haemoglobin synthesis. In some (e.g. thalassaemia) there is
inadequate production of the normal globin chains, and in others (e.g. HbS in sickle
cell disease) there is production of globin chains with an abnormal amino
acid sequence. They produce a variety of clinical problems mostly related to
anaemia and/or alteration in the solubility (HbS) or oxygen affinity of the abnormal haemoglobin (Chapter 8).
Congenital influences on respiratory
disease: several important
respiratory diseases that are discussed in detail in other chapters have
definit or implied genetic components, including asthma (Chapter 24), chronic
obstructive pulmonary disease (Chapter 26), emphysema (Chapter 26), cystic
fibrosi (Chapter 34) and pulmonary arterial hypertension (Chapter 27). Other
genetically linked diseases that cause pathological problems primarily in the
lung are listed in Fig. 17d.
