Lung and diaphragm development

Embryonic and fetal periods

• The embryonic period runs from fertilisation to the end of week 8; this is organogenesis, when malformations arise.
• The fetal period begins at the start of week 9 and is mainly growth and maturation. The lungs are one of the last organs to mature, which is why prematurity is a respiratory problem.

Lung bud

• The respiratory diverticulum (lung bud) grows from the ventral wall of the foregut in week 4.
• Tracheo-oesophageal ridges fuse into the tracheo-oesophageal septum, separating the trachea in front from the oesophagus behind. Incomplete division gives oesophageal atresia with tracheo-oesophageal fistula (commonest: blind upper pouch with a distal fistula).
• Airway epithelium and glands come from endoderm; cartilage, smooth muscle, connective tissue and vessels from splanchnic mesoderm; visceral pleura from splanchnic mesoderm and parietal pleura from somatic mesoderm.
• The bud splits into two bronchial buds (week 5), the right forming three lobar bronchi and the left two; by week 7 the segmental bronchi exist.

Stages of lung development

• Conducting zone: trachea to terminal bronchioles (anatomical dead space, no gas exchange).
• Respiratory zone: respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli.
• Fetal lungs are full of fluid secreted by the epithelium; fetal breathing movements and adequate amniotic fluid are needed for growth. At birth labour catecholamines switch the epithelium to absorb fluid; babies born by elective caesarean are more prone to transient tachypnoea of the newborn.

Surfactant

• Made by type II pneumocytes, stored in lamellar bodies (their characteristic ultrastructural feature) and released by exocytosis onto the alveolar surface.
• Main component dipalmitoylphosphatidylcholine (lecithin), with phosphatidylglycerol and surfactant proteins A–D.
• It lowers surface tension by placing phospholipid molecules between surface water molecules. Effects: prevents alveolar collapse at end-expiration, increases compliance (less work of breathing), stabilises small and large alveoli together (otherwise, by Laplace, small alveoli would empty into large ones), and keeps alveoli dry.
• Production is adequate by about 34–35 weeks. A lecithin:sphingomyelin ratio above 2 in amniotic fluid (or presence of phosphatidylglycerol) shows maturity.
• Steroids speed it up; insulin slows it down.

Neonatal respiratory distress syndrome

Complications include bronchopulmonary dysplasia and, from high oxygen, retinopathy of prematurity.

Development of the diaphragm

• The septum transversum begins at the level of the cervical somites, and muscle cells migrate in from C3–C5, bringing the phrenic nerve. As the diaphragm descends it drags the nerve with it, which is why diaphragmatic irritation refers pain to the shoulder (C4).

Congenital diaphragmatic hernia

• Bochdalek hernia (about 85–90%): defective or incompletely formed pleuroperitoneal membrane leaving the pleuroperitoneal canal open posterolaterally at the lumbocostal triangle; usually left (the left canal closes later and the liver protects the right).
• Gut enters the chest while the lungs are developing, so the main cause of death is pulmonary hypoplasia (both lungs, worse on the affected side) with pulmonary hypertension.
• Newborn: respiratory distress, scaphoid abdomen, bowel sounds in the chest, heart sounds shifted to the right. Often found on antenatal ultrasound.
• Management: intubate early (avoid bag-and-mask, which inflates the gut in the chest), nasogastric decompression, stabilise, then delayed surgical repair.
• Morgagni hernia: anterior, retrosternal defect between sternal and costal parts, usually right, small, may present late.
• Eventration: thin, muscle-poor diaphragm that bulges up but is intact.
• Congenital hiatal hernia: a short oesophagus pulls the stomach up.

Other lung anomalies

• Pulmonary hypoplasia also follows oligohydramnios (renal agenesis, Potter sequence) and small chest wall.
• Pulmonary sequestration: non-functioning lung with no bronchial connection and a systemic arterial supply from the aorta.
• Congenital pulmonary airway malformation: cystic overgrowth of terminal bronchioles.
• Bronchogenic cyst: abnormal budding, usually mediastinal near the carina.

Remember Lungs mature last: surfactant from about 24 weeks, enough by 34–35, alveoli keep forming until about 8 years.

Exam trap Surfactant increases compliance; its absence decreases compliance and collapses alveoli.

Exam trap Congenital diaphragmatic hernia kills through pulmonary hypoplasia, not bowel obstruction.

How FCPS asks about this

• Cells producing surfactant and their marker organelle: type II pneumocytes; lamellar bodies.
• Effect of surfactant deficiency: raised surface tension, decreased compliance, atelectasis; ground-glass X-ray.
• Cause and commonest site of congenital diaphragmatic hernia: defective pleuroperitoneal membrane; left posterolateral (Bochdalek, lumbocostal triangle).
• Main cause of death in CDH: lung hypoplasia with pulmonary hypertension.
• Zone containing terminal bronchioles: conducting zone; gas exchange begins at respiratory bronchioles.
• Start of the fetal period: beginning of week 9.
• Maternal condition delaying surfactant: diabetes (insulin); steroids accelerate it.