title: Studies on pulmonary alveoli: the effect of lung volume and of hyperventilation
Creators: name: Forrest, James Boyd
Publisher: name: University of Glasgow
Year: 1969

description: The surface tension properties of the internal lung surface play 6 significant role in the mechanics of respiration, by promoting stability of the air spaces. Hyperventilation has been shown by other workers to reduce pulmonary surface activity and cause instability of the alveoli. During the course of this study it was realised that the shape and size of alveoli were of great importance when evaluating alveolar stability, and that much more work was needed to establish the dimensional changes of alveoli occurring during the respiratory cycle, in the normal lung. In this thesis the methods available for studying pulmonary surface activity are reviewed and the evidence that a specific surfactant is responsible for the peculiar surface tension properties of the lungs, is critically examined. The few existing publications of studies on the shape and size of alveoli are assessed. PART 1 deals with studies on pulmonary surface activity in the normal lung and following a period of hyperventilation, in the guinea pig. Several methods were used, 1. pressure-volume manoeuvres during air filling. 2. measurement of lung compliance and calculation of the lung stability index. 3. examination of stable lung bubbles and the calculation of bubble stability ratios. 4. fluorescent microscopy for assessing lung autofluorescence and the fluorescence of stable lung bubbles. RESULTS; Hyperventilation caused the following: 1. the deflation curve of the pressure-volume relationship was less sigmoid, and the pressure required to maximally inflate the lungs was increased. 2. lung compliance was reduced by 30%. 3. the lung stability index was reduced by 11%. 4. the lung bubble stability ratio was reduced by 11%. 5. autofluorescence of frozen unfixed sections of lung tissue was reduced, but the fluorescence of stable lung bubbles was unaltered. Thus hyperventilation caused an increase in the forces which have to be overcome during lung inflation and decreased the stability of the air spaces, resulting in a tendency to premature collapse of the lungs. PART 11 deals with the measurement of the shape and size of alveoli and alveolar ducts on thin microscopic sections of the lungs of guinea pigs which had been rapidly frozen. A technique was developed by which living anaesthetized guinea pigs could be artificially ventilated with a positive and negative cycle, and rapidly frozen at the instant of cessation of ventilation, at a preselected point on the respiratory cycle. The morphometric methods used are described in detail and the volume shrinkage due to processing of the lungs was evaluated. Two sets of experiments were carried out using these techniques: the normal respiratory cycle was interrupted at different degrees of inflation (l) after spontaneous breathing, (2) after a period of hyperventilation. RESULTS; The total number of alveoli as well as the total alveolar surface area were found to depend on body weight. Effect of lung volume. 1. the total volume of alveoli increased during lung inflation. 2. the total volume of alveolar ducts changed little during lung ' inflation until the lungs were 40% inflated; thereafter it increased steeply. 3. the total alveolar surface area increased steeply during lung inflation from low lung volumes, but levelled off when the lungs were more than 50% inflated. 4. the volume to surface ratio of alveoli was unaltered during lung inflation. Effect of hyperventilation. 1. the total alveolar volume was reduced but the total alveolar duct volume was unaltered. 2. the total alveolar surface area was reduced. The reduction was most marked at high degrees of lung inflation. The above effects of hyperventilation were related to the duration of hyperventilation. Electron microscopic evidence is produced demonstrating that the alveolar surface membrane is smooth whether the lungs are fully inflated or whether they are collapsed. The harmonic mean thicknes of the air-blood barrier was decreased by 33% when the lungs were fully inflated from a near collapsed state. The functional significance of these findings is discussed with particular reference to the role of pulmonary surfactant.