A model of postnatal formation of alveoli in rat lung.

In rats, and many other species, most lung alveoli are formed after birth. Septation of the large air saccules existing at birth has been considered as the main mechanism for alveoli formation. However, other undefined means of alveolarization have also been postulated to account for the large increase in gas-exchange surface area that takes place in the lung as the rat grows larger. Moreover, recent results show that the majority of alveoli in rat lung are formed by means other than septation of saccules existing at birth, but these mechanisms have not been identified up to the present. In this study, a mathematical model of alveolarization in rat lung is presented. The model is based on three postulates: (a) new saccules continue to be formed up to adulthood according to certain rules; (b) all these saccules subsequently septate generating a certain number of alveoli; (c) once formed, the saccules (and alveoli) do not change in volume, but newly-formed saccules are larger than the preceding ones according to a given law. The model accurately predicts the experimentally-known values at different ages of total alveolar volume, alveolar number, volume of the average alveolus, gas-exchange surface area, and alveolar volume distribution for normal rats and for rats in which septation is inhibited by treatment with dexamethasone or hypoxia during the early postnatal weeks of life.     

Distribution of pores within alveoli in the human lung

Usually the wall opposite the orifice of alveoli has been used to study interalveolar pores by scanning electron microscopy. To ascertain whether biased results may be obtained from this, the distribution of pores within alveoli was studied in human lungs. By the use of scanning electron photomicrographs, the number, major axes of pores, and proportional area of pores to the alveolar wall were estimated. The alveolar wall seen opposite the orifice was defined as the bottom wall. Average number of pores per alveolus was 13-21, and one-half of them was located in the bottom walls. The average length of major axes was 7-19 micron, and average area fractions were 0.8-5%. The distribution of the numerical density, area fraction, and size of pores was uniform regardless of their location within the alveolus and the size of alveoli. Thus pores can be compared using the bottom walls of alveoli. This will facilitate the study of the effects of age, smoking, and topography on pore size and frequency in humans.     

Heterogeneous capillary recruitment among adjoining alveoli

Pulmonary capillaries recruit when microvascular pressure is raised. The details of the relationship between recruitment and pressure, however, are controversial. There are data supporting 1). gradual homogeneous recruitment, 2). sudden and complete recruitment, and 3). heterogeneous recruitment. The present study was designed to determine whether alveolar capillary networks recruit in a variety of ways or whether one model predominates. In isolated, pump-perfused canine lung lobes, fields of six neighboring alveoli were recorded with video microscopy as pulmonary venous pressure was raised from 0 to 40 mmHg in 5-mmHg increments. The largest group of alveoli (42%) recruited gradually. Another group (33%) recruited suddenly (sheet flow). Half of the neighborhoods had at least one alveolus that paradoxically derecruited when pressure was increased, even though neighboring alveoli continued to recruit capillaries. At pulmonary venous pressures of 40 mmHg, 86% of the alveolar-capillary networks were not fully recruited. We conclude that the pattern of recruitment among neighboring alveoli is complex, is not homogeneous, and may not reach full recruitment, even under extreme pressures.     

Breakdown of the cortical alveoli of medaka eggs at the time of fertilization,with a particular reference to the possible role of spherical bodies in the alveoli

Summary The process of cortical change upon fertilization of eggs of the teleostean fish,Oryzias latipes was investigated. A cortical alveolus (CA) contains colloidal material, a spherical body, and often a membranous structure. Upon insemination, breakdown of the cortical alveoli and elevation of the chorion began around the animal pole and ended at the vegetal pole. It was found that the spherical body was extruded with the colloidal material from the CA: the spherical body swelled after the opening of an aperture and was extruded into the perivitelline space through a large aperture. The empty CA shrank and disappeared completely as a result of the transformation of its envelope to numerous microvilli. The spherical body isolated or in the perivitelline space could be digested quickly by proteolytic enzymes. When spherical bodies in the perivitelline space of a fertilized egg were digested enzymatically, the vitellus came into direct contact with the chorion. The present study seems to show that swollen spherical bodies derived from CA play a role in maintaining a certain distance between the chorion and the vitellus after fertilization.     

Leukocyte trafficking in alveoli and airway passages

Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circulation, whereas the pulmonary circulation feeds the distal lung parenchyma. The presence of different cell types in large airways from those in alveoli might contribute to site-specific differences in the molecular regulation of the inflammatory process.     

Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships

To determine alveolar pressure-volume relationships, alveolar three-dimensional reconstructions were prepared from lungs fixed by vascular perfusion at various points on the pressure-volume curve. Lungs from male Sprague-Dawley rats were fixed by perfusion through the pulmonary artery following a pressure-volume maneuver to the desired pressure point on either the inflation or deflation curve. Tissue samples from lungs were serially sectioned for determination of the volume fraction of alveoli and alveolar ducts and reconstruction of alveoli. Alveoli from lungs fixed at 5 cmH2O on the deflation curve (approximating functional residual volume) had a volume of 173 X 10(3) microns3, a surface area of 11,529 microns2, a mouth opening diameter of 72.7 microns, and a mean caliper diameter of 91.8 micron (SE). Alveolar shape changes during deflation from total lung capacity to residual volume was first (30 to 10 cmH2O) associated with little change in the diameter of the alveoli (102.7 +/- 2.4 to 100.3 +/- 3.3 microns). In the range overlapping normal breathing (10 to 0 cmH2O) there was a substantial decrease in diameter (100.3 +/- 3.3 to 43.3 +/- 2.3 microns). These measurements and others made on the relative changes in the dimensions of the alveolus suggest that the elastic network, particularly around the alveolar ducts, are predominant in determining lung behavior near the volume expansion limits of the lung while the elastic and surface tension properties of the alveoli are predominant in the volume range around functional residual capacity.     

Biphasic mode of epithelial regeneration in murine pulmonary alveoli

After administration to mice of butylated hydroxytoluene, the pulmonary alveolar epithelium adopts a biphasic pattern of regenerative proliferation. This hitherto-unnoticed pattern of epithelial repair in the lung was revealed by the investigation of stereologic parameters. The earliest evidence of epithelial injury involved the type I pneumocytes, whose necrosis and disappearance from the septal surface was shown by a lowered surface density (SV). Proliferation of the type II pneumocytes ensued: the volume density (VV) rose above normal soon after the onset of necrosis, only to decrease as the cells slowly differentiated into intermediate and then type I pneumocytes. A second peak of type II pneumocytes appeared as the denuding of septa persisted. This twofold proliferation was also shown by the numerical density count (NV). Differentiation into an intermediate pneumocyte was itself documented by the raised VV and SV values. These observations of a biphasic mode of proliferation of type II pneumocytes raise the question of an unsuspected, persistent action of the toxic agent within pulmonary alveoli and serve to document the homeostasis of epithelial regeneration.     

Lung alveoli: endogenous programmed destruction and regeneration

Mammalian alveoli, complex architectural and cellular units with dimensions that are linked to the organism's O2 consumption (VO2), are thought to be destroyed only by disease and not to spontaneously regenerate. Calorie restriction of adult mammals lowers VO2, and ad libitum refeeding returns VO2 to pre-calorie-restriction values. We took advantage of these relationships and tested the hypothesis in adult mice that calorie restriction (two-thirds reduction for 2 wk) followed by ad libitum refeeding (3 wk) would cause alveolar destruction and regeneration, respectively. Calorie restriction diminished alveolar number 55% and alveolar surface area 25%. Refeeding fully reversed these changes. Neither manipulation altered lung volume. Within 72 h, calorie restriction increased alveolar wall cell apoptosis and diminished lung DNA (approximately 20%). By 72 h of refeeding, alveolar wall cell replication increased and lung DNA rose to amounts in mice that were never calorie restricted. We conclude that adult mice have endogenous programs to destroy and regenerate alveoli, thereby raising the danger of inappropriate activation but the possibility of therapeutic induction, if similar programs exist in humans.     

An electron microscopic study of the acid mucosubstance lining the alveoli of hamster lung

Synopsis Hamster lung has been investigated by electron microscopy using colloidal iron oxide and Ruthenium Red stains. A continuous layer of acid mucosubstance has been demonstrated on the surface of the alveolar epithelial cells. The lining layer associated with the membranous pneumonocytes has been found to be consistently thinner than that covering the granular pneumonocytes and alveolar macrophages. Strong binding of stain has also been observed in osmiophilic membranous material which is thought to represent fragments of pulmonary surfactant. The susceptibility of the alveolar lining material to digestion by neuramidase suggests that it consists mainly of a sialomucin.