1. All you need to know about the lungs Dr David Lacy

2. A little about me… Consultant General Paediatrician with a respiratory interest at Arrowe Park Hospital Trained in respiratory paediatrics in Birmingham and Liverpool Been a consultant for 14 years Arrowe Park Hospital is a DGH for the Wirral Total population 320,000 of whom 60,000 are children. Births per year 3200. Have speciallist clinics in asthma, cystic fibrosis, chronic lung disease (of prematurity) and allergy.

3. Cases of diffuse lung disease that I have seen Currently look after 28 children with Cystic fibrosis Currently 10 patients with non CF bronchiectasis Currently 5 patients with bronchiolitis obliterans (10-12 in total) 3 patients with ILD (one of whom has moved away) 1 patient with primary ciliary dyskinesia

4. Overview Embryology Lung development: Prenatal Postnatal Lung structure Alveolar cells and pulmonary surfactant Investigations, X-rays and CT scans Pathogenesis

5. 0-6 wk 6-16 wk 16-24 wk 24-40wk 36 wk – 2yr Embryonic Pseudo Canalicular Saccular Alveolar glandular

6. Embryonic 4 th week: lung bud oesophagus 6 th week: lobar & segmental airways NB Tracheo-oesophageal fistula can occurr at this stage Lung and gut development closely linked

7. Pseudoglandular: 6-16 weeks Conducting airways complete by wk16 20 generations (branches) to acinus (very simple air sac) Blood supply starts to form Cells become speciallised

8. Canalicular: 16-24 weeks Acinus appears (buds) (respiratory zone) multiplication of capillaries Alveolar cells become speciallised

9. Saccular: 24-40 weeks Terminal air sacs form True alveoli 32wks onwards Complex capillary network forms Thinning of blood-air barrier

10. Postnatal lung development Alveolar period 36/40 – 2 years At birth simple alveoli present 85% alveoli develop after birth Alveolar cell Type I Alveolar cell Type II

11. Postnatal lung development Alveolar period 36/40 – 2 years 5 million at birth 300 million at 2 years

12. Premature birth Alveoli units not fully developed Air-blood barrier thick → inefficient gas exchange <32wks no true alveoli immature surfactant system (alveolar collapse) underdeveloped surface area gas exchange chest wall very soft - recession

15. Gross Anatomy of the Lungs Cardiac Notch Left Lower Lobe Left upper Lobe

17. Alveolar cells Type I o 95% of alveolar surface o Long and thin- ideal for gas exchange Type II o More numerous but only 5% on surface o Large cuboidal cells with microvilli o Surfactant production

18. Pulmonary Surfactant Pulmonary surfactant forms a thin fatty layer that coats the airways of the lung and is essential for proper inflation and function of the lung. Pulmonary surfactant is composed of 90% phospholipid (special fat substance) and 10% protein Surfactant is produced by alveolar type II cells, stored inside special structures called lamellar bodies, and actively secreted in the alveoli. Upto 10% of children with ILD have now been found to have a surfactant deficiency due to mutations of surfactant B, C or ABCA3

19. Surfactant Proteins Proteins constitute approx 10% of Surfactant AInvolved in host immune response* BRequired for spreading and stability of surfactant film CRequired for spreading and stability of surfactant film DInvolved in host immune response* * Fighting infection

20. ABCA3 Full name is ATP-binding cassette transporter A3 It is in alveolar type II cells. It transports lipids (fats) to the lamellar bodies (special unit within the cell) where the fats are used to assemble surfactant and then the surfactant is transported to the cell surface. Mutations of the gene that code for this protein can occur. If a baby has two faulty copies (one from each parent) this results in insufficient surfactant production and ILD.

21. Investigations CXR CT scan Bronchoscopy Biopsy Genetic tests

26. Pathogenesis of ILD Damage to the alveoli o Persistent inflammation o Disordered repair of damage cells- leading to fibrosis* o Disordered cell function and growth *ILD is sometimes called Fibrosing alveolitis. Interstitium refers to the tissues around the alveoli.

27. Conclusions Lung disease can effect the airways, the alveoli, or the surrounding structures (called the interstitium) Lungs grow in 3 phases o Early prenatal development o Birth -2years increase in number of alveoli o 2 years to adulthood- growth in size of alveoli Surfactant is produced in type II alveolar cells and without surfactant the alveoli collapse and cannot function properly