eMedicine Specialties > Radiology > Pediatrics

Pulmonary Hypoplasia

Author: Prabhakar Rajiah, MD, MBBS, FRCR, Registrar, Department of Radiology, Central Manchester and Manchester Children's University Hospitals, UK
Contributor Information and Disclosures

Updated: Sep 26, 2008

Introduction

Background

Pulmonary hypoplasia is a developmental abnormality of the lung characterized by a decrease in the number of alveoli, cells, and airways, eventually resulting in decreased size and weight of the lungs. Although pulmonary hypoplasia is occasionally a primary condition, most cases are secondary to other abnormalities that prevent complete pulmonary development. Pulmonary hypoplasia is frequently associated with malformations of the cardiac, genitourinary, gastrointestinal, and musculoskeletal systems. Bronchopulmonary malformations are also associated with this disease.^{1,2,3,4,5,6,7,8,9}

Related eMedicine topics:
Pulmonary Hypoplasia (Pediatrics)
Bronchopulmonary Dysplasia

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Pathophysiology

FACTORS REQUIRED FOR NORMAL LUNG DEVELOPMENT 

Several factors are required for normal development of the lung:

• First, a normal volume and pressure relationship between the lung and amniotic fluid is needed. The lung fluid volume depends on the balance between fluid secreted by the lungs and fluid exiting into amniotic fluid. Tracheal pressure is normally higher than that of the amniotic fluid.
• Second, lung fluid factors or growth factors, such as peptide growth factors and thyroid transcription factor-1, are essential for proper lung development.
• Third, renal factors are needed. Proline secreted by the renal tubules is essential for the development of collagen and the mesenchyme of the lung. Hence, fetal urine is essential for pulmonary development.

Pulmonary hypoplasia is pathologically characterized by a decreased number of acini due to a decreased number of branching generations or decreased size of the alveoli. Unlike agenesis or aplasia, pulmonary hypoplasia results in bronchi and alveoli that are intact. The pulmonary artery is usually small or, sometimes, absent. Surfactant deficiency and delayed or absent epithelial differentiation are seen.¹⁰

CAUSES OF PULMONARY HYPOPLASIA

Primary pulmonary hypoplasia can occur without any clear cause.

Pressure effect on the developing lung

• (Any condition that restricts lung expansion during fetal life is a cause of pulmonary hypoplasia.)
• Cystic adenomatoid malformation
• Diaphragmatic hernia
• Eventration of diaphragm
• Sequestration of lung
• Pleural effusion
• Chylothorax
• Hydrops fetalis
• Ascites
• Cardiac mass
• Mediastinal mass
• Cystic hygroma
• Abdominal mass

Restricted thoracic expansion

• Jeune syndrome (asphyxiating thoracic dystrophy)
• Achondroplasia
• Thanatophoric dwarfism
• Osteogenesis imperfecta
• Chondroectodermal dysplasia

Impaired fetal breathing

• CNS lesions (brainstem or spinal cord)
• Arnold-Chiari malformations
• Anencephaly
• Hypoxic lesions
• Bulbar palsy
• Respiratory depressants
• Phrenic nerve lesions
• Neuromuscular disorders
• Arthrogryposis congenita multiplex
• Congenital myotonic dystrophy
• Pena Shokeir syndrome

Decreased pulmonary flow

• Tetralogy of Fallot
• Ebstein anomaly
• Aplasia/hypoplasia of the pulmonary artery
• Pulmonary stenosis
• Hypoplastic right heart
• Scimitar syndrome

Oligohydramnios

• Renal agenesis
• Renal dysplasia
• Renal cystic disease/hydronephrosis
• Bladder outlet obstruction
• Amniotic fluid leak
• Prolonged rupture of the membranes

Acquired causes

• Infection (Swyer-James syndrome)
• Aspiration
• Radiation
• Surgery
• Scoliosis

Primary/idiopathic causes

• Trisomy 18, 13, or 21
• Familial

Scimitar syndrome

Pulmonary hypoplasia is also a component of the Scimitar syndrome (congenital venolobar syndrome, hypogenetic lung syndrome), the components of which are the following: 

• An aberrant vein draining the right lower lobe into the subdiaphragmatic inferior vena cava
• Pulmonary hypoplasia
• An aberrant vascular supply from the aorta
• Dextrocardia

OTHER ASSOCIATIONS OF PULMONARY HYPOPLASIA

• Abdominal wall defects
• Hemolytic disease of the newborn
• Down syndrome
• Neonatal hypophosphatasia
• Glutaric acidemia (type II)
• Laryngotracheoesophageal cleft
• Cloacal dysgenesis
• Spinal deformities
• Deformed thumb
• Ventricular inversion

PATHOLOGY

The hypoplastic lung has decreased airway generations and acini and decreased alveolar size. A combination of the 2 can also be seen.

Frequency

United States

The incidence of pulmonary hypoplasia is approximately 13%, with a range of 9-28%.

International

The worldwide incidence of pulmonary hypoplasia is 3-28% in cases of premature rupture of membranes at 15-28 weeks.

Mortality/Morbidity

Mortality rates of pulmonary hypoplasia are high during the neonatal period, and 71-95% of deaths are due to severe respiratory compromise. The mortality rate is higher in cases involving premature deliveries, marked oligohydramnios, or premature rupture of the membranes.

Pneumothorax and respiratory distress are common in these infants.

A lethal type of pulmonary hypoplasia is acinar aplasia, where the alveolar ducts are not developed, resulting in the absence of gas exchange and early death.

Age

The majority of cases of pulmonary hypoplasia occur during the perinatal period, with respiratory distress.

Anatomy

NORMAL DEVELOPMENT OF THE TRACHEOBRONCHIAL TREE AND LUNG

The development of lung proceeds in many stages from the third week of intrauterine life until 2 years after birth. The lung bud divides into right and left branches by 28 days, and segmental bronchi are formed by 30 days. Progressive branching takes place from this stage. The right lung divides faster than the left and has more branches.

STAGES IN LUNG DEVELOPMENT

The 5 stages in the development of the lung are the embryonic period, the pseudoglandular period, the canalicular period, the saccular period, and the alveolar period.

Embryonic period (first 7 weeks)

The lung bud originates from the ventral aspect of the primitive foregut, at the level of the pharynx, as a small medial bulge during days 24 through 36 of development. The mesoderm proliferates in the primitive mesentery, which contributes to the muscles, connective tissues, and cartilage of the tracheobronchial tree and the lung, while the epithelium originates from the endoderm. The vascular supply of lung, which until 30 days is from the splenic plexus, shifts to the pulmonary arteries. The pulmonary venous system forms from the capillary plexus in the mesenchyme, which eventually fuses with the pulmonary arterial system. This venous system anastomoses with the central pulmonary veins arising from the sinoatrial region and eventually drains into the left atrium.

Pseudoglandular period (weeks 5-17)

The lung looks like a gland during this stage, extending into the surrounding mesenchyme, which is solid. All future nonrespiratory airways are formed toward the end of this period. Cartilage is formed in the trachea and proximal bronchi at around 10 weeks and in the segmental bronchi at 16 weeks. The bronchi have no lumina at this stage.

Canalicular period (weeks 17-26)

During the canalicular stage, the peripheral tubules open and widen. The cuboidal epithelium differentiates into type I and type II epithelial cells; type II epithelial cells produce the surfactant. Thin air-blood barriers are formed at this stage, and the number of generations of distal airways is gradually reduced, as some of the terminal bronchioles become converted into respiratory bronchioles, with conversion of the lining epithelium. Preacinar vessels and intra-acinar vessels develop to supply the acini; they arise from the pulmonary artery, which in turn is derived from the sixth aortic arch.

Saccular period (week 26 until birth)

This stage is characterized by progressive development of pulmonary parenchyma and a decrease in the amount of connective tissue. The saccules continue to divide and become smaller, with thinner walls. The surfactant system further matures. At birth, the alveoli are not completely formed, and the lungs are immature. Gas exchange takes place through transitory ducts and saccules. The septa are thick, with a double layer of capillaries, and gas exchange is limited. Alveoli appear from 32 weeks onward.

Alveolar period (birth to 3 years of age)

The alveoli progressively develop by means of septal formation. The septa are thin and have a single layer of capillaries. The gas-exchange area of the lung progressively increases, and the alveoli are continually formed and become bigger until about 300 million are formed at 8 years of age. Continuous development of the intra-acinar arteries also occurs.

Presentation

The clinical features of pulmonary hypoplasia are variable depending on the age of presentation, the severity of the disease, and the presence of associated malformations.

In the neonatal period, the disease is usually severe and presents as respiratory failure. Occasionally, the onset is delayed, and patients present with difficulty in breathing, cyanosis, frequent respiratory infections, and growth retardation.

On examination, the affected thorax is usually small; the mediastinum is shifted to the same side; percussion is dull because of displacement of mediastinal structures or resonant due to pneumothorax; and breath sounds are reduced. Associated skeletal and cardiac malformations can be detected.

Other problems to consider are atelectasis, persistent pulmonary hypertension, pulmonary agenesis, and pulmonary aplasia. In pulmonary agenesis, the lung is absent, as are the bronchi, airways, and pulmonary vasculature. The right and left sides are affected equally. The prognosis is worse if the right side is involved because of associated severe congenital malformations. The affected side has reduced volume. Patients have homogeneous opacification of the entire lung, with a mediastinal shift to the same side. Compensatory overinflation of the opposite lung and herniation and congenital malformation are associated findings. In pulmonary aplasia, the lung is absent, but a rudimentary blind ending bronchus is present.^2,11

Preferred Examination

Antenatal ultrasonography provides early predictors of pulmonary hypoplasia.^12,13

MRI is used in some centers to assess fetal volume and predict the presence of pulmonary hypoplasia.¹⁴

After birth, chest radiography shows changes of pulmonary hypoplasia, which is better demonstrated on CT scans. Any vascular abnormality is also assessed with CT or contrast-enhanced magnetic resonance angiography.

Differential Diagnoses

Other Problems to Be Considered

Atelectasis
Persistent pulmonary hypertension
Pulmonary agenesis
Pulmonary aplasia
Proximal interruption of pulmonary artery.

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