Terminal Air Spaces Research Articles

Scanning electron microscope study of the development of the human respiratory acinus.

Plastic corrosion casts were made of lungs from fetuses aged from 19 weeks' gestation to term and of lungs from a child and two adults to study the development of the respiratory acinus. To achieve reliable infusion of the most peripheral airspaces a high viscosity plastic was used that is not known to have been employed previously for corrosion casting of lungs. The casts were examined in the scanning electron microscope and showed the increase both in number and in length of the airways distal to the terminal bronchiole and also the change in shape and complexity of the most peripheral airspaces as the lung matures. The terminal airspaces change from short, simple, tubular endings at 19 weeks' gestation to short, shallow saccules from around 30 weeks' gestation to full term and contrast with the deep cup shaped alveoli in the adult. Measurements of the size of the terminal airspace at various stages of development are presented. This new approach, allowing three dimensional study of the peripheral airspaces of the developing lung, will be useful for investigating the lung pathology of neonates.

Castration prolongs tolerance of young male rats to pulmonary O2 toxicity.

We tested the hypothesis that the normal loss of tolerance of neonatal rats to prolonged hyperoxic exposure at around 1 mo of age might be related to the marked increase in sex hormones occurring around this period. Male rats castrated at 20 days of age demonstrated significantly increased survival in greater than 95% O2 compared with sham-operated rats when exposed to high O2 at various ages greater than 45 days [castrated, 115 of 166 (69%) vs. sham, 59 of 156 (38%) (P less than 0.001)]. Testosterone replacement led to survival rates comparable with sham-operated rats [30 of 87 (34%)]. No such protective effect was observed in female rats [survival: ovariectomy, 16 of 33 (48%) vs. sham, 14 of 28 (50%)]. The improved survival in the older castrated males was not associated with an increase in lung antioxidant enzymes, which is normally seen in O2-tolerant neonatal rats. Castration did result in marked morphological lung changes, including significantly enlarged lung volumes (4.54 +/- 0.72 vs. 3.76 +/- 0.29 ml/100 g) and terminal air spaces [mean linear intercept (LM) = 51.6 +/- 5.0 vs. 46.3 +/- 4.1 micron (P less than 0.001)]. Testosterone replacement also prevented these morphological changes. The altered lung growth 1) may be related to the influence of other endocrine imbalances after castration and 2) may be an important factor in the relative O2 tolerance of the castrated male rats beyond the neonatal period.

Subclinical Effects of Smoking: Physiologic Comparison of Healthy Middle-aged Smokers and Nonsmokers and Interrelationships of Lung Function Measurements

Measurements of ventilatory function, distribution of ventilation, diffusing capacity, and lung mechanics were made on healthy middle-aged smokers and nonsmokers drawn from a randomly selected population in order to assess the effects of cigarette smoking and the interrelationships of the several indices of lung function. Although very few subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. For the total group studied, there were significant correlations between various indices of function. A significant proportion of the variance in diffusing capacity and in diffusing capacity per liter of lung volume can be accounted for by an index of lung recoil which may, in turn, be related to size of terminal air spaces.

ENDOTOXIN ALTERS MORPHOMETRIC PATTERN OF LUNG REGROWTH IN PNEUMONECTOMIZED RATS

We have previously demonstrated that a low dose of endotoxin (ENDO) alters the biochemical response of adult rats postpneumonectomy (PX) towards the pattern seen post-PX in young animals (i.e. increase in lung RNA and RNA/DNA ratio)(Peds. Res. 17:390A, 1983). To determine whether ENDO also alters the morphologic pattern of lung regrowth, we performed left pneumonectomies on adult rats, followed 24 hrs later by ENDO (250μg/kg) or saline injection, i.p. Lungs were formalin-fixed (20cmH20 inflation pressure) at 3 days post-op. The percent increases in right lung volume at 3 days post-PX was 48±10% for ENDO-PX compared to a control group and 23±14% for saline-PX, p<0.05. Microscopically the ENDO-PX lungs had obviously enlarged terminal air spaces compared to controls or the saline-PX group. Morphometric evaluations confirmed this impression:Saline pressure-volume curves, with volume expressed as percent of total lung capacity (at 20cmH20) were not different between ENDO-PX and saline-PX rats. We conclude that adult rats subjected to PX followed by ENDO treatment have an altered pattern of lung regrowth (consisting of large air spaces without a decrease in ISA), not explained by differences in tissue compliance.

Creation and repair of diaphragmatic hernia in the fetal lamb: Lung develpment and morphology

Left-sided diaphragmatic hernias were created in 26 lambs at about 78 days' gestation and repaired at 106 to 124 days' gestation. Nine of these lambs were delivered at term and lived much longer than the nonrepaired lambs delivered at term. The normal development of the fetal lamb lung is compared and contrasted with the development of the lung after creation of a diaphragmatic hernia and also with the changes in morphology resulting from in-utero repair. Creation of a diaphragmatic hernia resulted in marked delay in the development of alveoli and at term the lung had small, thick-walled terminal air-spaces with few capillaries and no true alveoli when compared with the thin-walled alveoli in normal lungs. Another striking feature was an apparent increase in the frequency of type II alveolar cells in diaphragmatic hernia lungs. In-utero repair of the diaphragmatic hernia resulted in a more normal appearance with true alveoli developing by term, although capillaries appeared to be less numerous and type II cells more numerous than in normal lungs. Surprisingly, there appears to be little difference between the left and right lungs in lambs with diaphragmatic hernia.

Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque

To test the effect of dose and time on fetal lung maturation by exogenous glucocorticosteroids, triamcinolone acetonide was given to time-mated pregnant rhesus macaques (Macaca mulatta). Triamcinolone acetonide (10 mg/kg or 1 mg/kg) was administered intramuscularly during the midpseudoglandular (63 to 65 days' gestational age) or midcanalicular phase (110 to 112 days' gestational age) of lung development. Fetectomies were performed at 90, 120, or 150 days' gestational age. Nontreated control fetuses and postnatal animals from 59 days' gestational age to 31 days' postnatal age were collected for study of normal developmental lung morphology in the rhesus monkey. Lungs from fetuses of 90 days' gestational age and older were fixed by tracheal infusion, and lungs from fetuses less than 90 days' gestational age were fixed by immersion and embedded for high-resolution light microscopy. Body weight, crown-rump length, and fixed lung volume were determined for all fetuses. Morphometric evaluation of the volume percent of parenchyma, the volume percent of air space and the mean linear intercept as an estimate of air space size was also done. Lungs from fetuses treated during the canalicular phase had thinner, longer, less cellular septa, larger air spaces, and increased numbers of alveolar divisions in terminal air spaces as compared to those of controls. Lungs of fetuses treated during the pseudoglandular phase also had some septa which were thinner, less cellular, and longer than those of controls and had a marked increase in air space size. However, most septa were greatly reduced in height and appeared fewer in number. Alveolar divisions were decreased. The volume percent of air space was larger in all treated groups. Fixed lung volume normalized to body size (body weight and crown-rump length) was greater than that for controls for the high-dose canalicular phase treatment group. The same parameter was lower than that of controls for the high-dose, pseudoglandular phase treatment group of 150 days' gestational age. Body weight and crown-rump length for all pseudoglandular phase triamcinolone acetonide-treated fetuses also tended to be lower than those of controls. We concluded that: (1) there is both a time-dependent and a dose-dependent effect on triamcinolone acetonide on fetal lung maturation in rhesus macaques, (2) triamcinolone acetonide accelerates maturation of the interstitial and epithelial component of the developing fetal rhesus lung independent of age, (3) triamcinolone acetonide accelerates alveolarization only at later treatment ages, and (4) triamcinolone acetonide induces retardation of growth of some of the lung septa and body growth only

Effect of terbutaline on lung mechanics and morphology in the preterm rabbit neonate.

Lung morphology, surface properties of fetal pulmonary fluid, and lung mechanics during spontaneous breathing were studied in preterm newborn rabbits after antenatal administration of terbutaline (0.1 mg). The histological evaluation of lung sections revealed increased amounts of granular eosinophilic and sudanophilic material in the terminal airspaces. The amount of fetal pulmonary fluid was decreased in terbutaline-treated animals; the fetal pulmonary fluid also showed improved surface properties, evaluated by the pulsating bubble technique. Increased dynamic lung compliance without altered air-way resistance was found in terbutaline-treated animals during the first 30 min after onset of breathing. This report demonstrates that terbutaline has an initial beneficial influence on the preterm neonatal lung, probably due to release of preformed surfactant into the alveolar spaces and to dehydration of the lung.

Pulmonary mechanics in dogs given different doses of kerosene intratracheally.

Kerosene was instilled intratracheally into mongrel dogs of either sex weighing 10 to 15 kg and anesthetized intravenously with sodium pentobarbital (25 mg/kg). Two different doses were used: 0.3 and 0.06 ml/kg. Pulmonary mechanics, including pressure-volume (P-V) curve, thoracic gas volume (Vtg), total lung capacity (TLC), total pulmonary resistance (RL), and chord compliance (CL) were measured by using a whole body plethysmograph, before and at various time intervals during the 2 wk after instillation. Histologic studies were also performed. In the high-dose (0.3 ml/kg) kerosene experiments there were significant decreases in Vtg, TLC, and CL values by 24 h, which returned to control values at 1 wk after kerosene instillation. The RL and CL normalized for TLC did not change. In contrast, in the dogs receiving the low dose (0.06 ml/kg), there was no significant change in any of these parameters at 24 h. Histologic examination revealed an early exudative phase consisting of exudation of macrophages, red cells, and edema (at 1 and at 24 h), and a later phase consisting of proliferative bronchiolitis (at 1 and at 2 wk). Animals receiving the low dose revealed the same pattern as those receiving the high dose at 24 h, but changes were less extensive. We conclude (1) that kerosene-induced lung injury causes loss of terminal air spaces at both low and high doses, and (2) that the shift in the P-V curve is dose dependent. We hypothesize that kerosene causes two types of physiologic lesions. In areas in which terminal air spaces remained open, an increase in compliance occurred, whereas in areas in which intraalveolar exudation occurred there was "drop-out" of lung units. The final P-V curve was determined by the relative proportions of these two types of areas.

Effect of positive end-expiratory pressure and body position in unilateral lung injury

Positive end-expiratory pressure (PEEP), by increasing lung volume in acute lung injury, may recruit terminal air spaces in the involved regions, but may also distend noninvolved regions increasing extravascular lung water and worsening gas exchange. We investigated the effect of increasing levels of PEEP on arterial oxygenation in 26 anesthesized dogs with unilateral acid pneumonitis and studied the influences of gravity and distribution of the injury on this effect. Arterial PO2 was consistently higher when the noninjured lung was dependent than in the supine or injured lung-dependent positions. Low levels of PEEP (5, 10 cmH2O) improved arterial oxygenation and reduced intrapulmonary physiological shunt. However, 15 cmH2O PEEP resulted in worsening of gas exchange, increased dead space ventilation, and diminished static compliance. The adverse effects of high levels of PEEP on arterial oxygenation were similar whether the injured lung was dependent or not and were evident a lower levels of PEEP in one group of dogs in which the unilateral injury was more diffuse and in which the upper and middle lobes were also involved. Thus, the compressive effects of high levels of PEEP on alveolar capillaries in the noninjured lung are influenced by the extent and distribution of injury in the injured lung, but not by local forces governing regional blood flow distribution.

Lung Development in the Fetal Primate Macaca Nemestrina. III. HMD

Delivery of M. nemestrina at 80% of normal gestation provides a population of neonates at high risk for hyaline membrane disease (HMD). The diagnosis of HMD was made by the presence of reticulogranular densities and air bronchograms on chest radiographs. Patchy atelectasis was seen in the lungs of animals assigned by clinical and radiographic criteria to the HMD group and not in the normal lungs of animals matched for gestational and postnatal age. Total phospholipid and phosphatidylcholine in whole lung, airway lavage fluid, and surface-active materials were lower in animals with HMD. Amniotic fluid L/S ratios were lower in the group that developed HMD. Pressure-volume measurements indicated decreased distensibility and unstable terminal air spaces in the HMD group. Alveolar-arterial oxygen pressure differences were greater in animals with HMD. There were no differences between HMD and normal groups in body weight, lung weight, percent dry lung weight, gestational age, and postnatal age at death. This primate species, subjected to premature delivery, is a suitable animal model of HMD in human neonates.

Expansion pattern of terminal air-spaces in the premature rabbit lung after tracheal deposition of surfactant.

The expansion pattern of the lungs of full-term and premature newborn rabbits was evaluated by direct observation of the lung surface during an inflation-deflation cycle, with particular reference to the effect of tracheal deposition of surfactant before the first breath. In non-treated premature fetuses, aeration of alveoli was initiated at an endotracheal pressure of 35 cm H2O; the mean corresponding 'opening pressure' was 25 cm H2O in both full-term and surfactant-treated premature animals. The process of alveolar aeration was asynchronous in all groups but at maximal inflation pressure (35 cm H2O) the expansion pattern was uniform in full-term and surfactant-treated premature fetuses; these animals also developed residual volume. In non-treated premature animals aeration was patchy, even at maximal inflation, and the lungs emptied at the end of deflation.

Effects of a molecular change in collagen on lung structure and mechanical function.

Semicarbazide, a lathyrogen, was given to growing rats to elucidate the consequences of altering the molecular structure of fibrous proteins within the lung. Static pressure-volume (P-V) measurements during deflation of saline-filled lungs showed normal recoil pressure and compliance values within the physiological range of lung volume. Quasi-static P-V measurements were also normal during slow reinflation, even beyond physiological limits to a recoil pressure of 20 cm H20. However, the lungs of experimental rats ruptured at much lower recoil pressures than controls. Histology was normal in lungs fixed at 20 cm H20. In contrast, lungs showed dilation of terminal air spaces, rupture of alveolar walls, and an increase in mean linear intercept in experimental compared with control specimens, when fixed at 30 cm H20. Biochemical analyses revealed reduced cross-linking of lung collagen without change in its total content. There were no detectable changes in the quantity or quality of lung elastin. It is concluded that semicarbazide may selectively impair the maturation of lung collagen and that immaturity of lung collagen is associated with a reduction in the tensile strength of lung tissue, without changes in elasticity within physiological volume limits.

“Hyaline membrane disease” in newborn infants: Macroscopic, Radiographic, and Light and Electron Microscopic Studies

Abstract o 1. This paper reviews the pathology of hyaline membrane disease using light and electron microscopy together with vascular injection experiments. Particular emphasis is placed on the ultrastructure of developing and neonatal lungs as compared to adult lungs. A sharp distinction is made between the air-blood barrier, the interalveolar septum, and the alveolar wall. 2. The appearance of the lungs differs in hyaline membrane disease depending on the postmortem interval. The classic radiologic appearance of the lungs is not present unless the lungs are re-expanded; increasing the postmortem interval produces a variable and uneven air expansion pattern and more prominent pulmonary edema. In addition, reparative and reactive changes occur if the children live any significant length of time. 3. Hyaline membranes are still the most reliable criterion for the diagnosis of hyaline membrane disease. These membranes are the result of increased plasma transudation, epithelial necrosis, and inhaled amniotic fluid. Fibrin is only exceptionally observed. 4. Pulmonary lymphatics are enlarged and distended in hyaline membrane disease. This study provided a unique opportunity to investigate the structure and function of human pulmonary lymphatics. 5. Postmortem vascular injection experiments show a filling defect involving the small muscular pulmonary arteries and the pulmonary arterioles although the pulmonary veins and venules are normal. 6. Lamellar bodies, considered to be related to the secretion of pulmonary surfactant, are present in the type II alveolar epithelial cells in hyaline membrane disease. Typical lamellar bodies and multivesicular bodies were also observed in the terminal air spaces of a fetus of 20 weeks' gestation. 7. There are multiple, apparently related mechanisms involved in the pathogenesis and outcome of the idiopathic respiratory distress syndrome, and it is not as yet certain which is primary. Important factors seem to be high pulmonary vascular resistance; impaired or deficient surfactant activity; increased alveolar wall permeability and transudation; and inhaled amniotic fluid. Secondary phenomena seem to be epithelial necrosis and hyaline membrane formation, lymphangiectasis and lymphatic congestion, interstitial and reparative phenomena, and pulmonary edema and pulmonary hemorrhage. 8. More data should be available about, and investigations directed toward, gestation, intrauterine development, and birth of infants with hyaline membrane disease as the disease seems not to start after birth but be induced before it.

The pattern of the terminal air spaces in a premature infant of 30-32 weeks that lived nineteen and a quarter hours.

AbstractThe availability of a perfectly preserved lung from a premature infant of 30–32 weeks that lived nineteen and a quarter hours has made possible the first wax reconstructions of the terminal air spaces in the canalicular period of fetal growth. Here, as in the newborn, the most distal respiratory bronchioles give rise to two pairs of clusters of saccules, but with this difference: each saccule (lined by flat epithelium) is separated from others by a spongy, vascular, connective tissue matrix. By reconstructing just the cavities of the saccules one can study the bizarre shapes presented by the saccules. In pattern the latter closely resemble peripheral alveolar saccules of the child lung modelled by the writer. Seemingly, therefore, this fetal period is the one in which the terminal generations of branches are being elongated and their shapes determined by invading capillaries and connective tissues. Clinically, one may conclude that peripheral diffusion of gases (in the infant or adult lung) does not follow any such simple dichotomous pattern of flow as has been hitherto assumed.

Idiopathic diffuse interstitial pulmonary fibrosis (fibrosing alveolitis), atypical epithelial proliferation and lung cancer

Areas of atypical epithelial proliferation were seen in the terminal airspaces in eight cases of idiopathic diffuse interstitial pulmonary fibrosis. These atypical changes included the presence of cuboidal and columnar epithelium characteristic of more proximal airspaces, squamous metaplasia in areas of predominantly cuboidal or columnar cells, and stratification of cells at times to a marked degree. In some areas nuclear and cytoplasmic changes suggested progression toward frank malignancy. Lung cancer was present in three of the eight cases. Two peripheral cancers included an adenocarcinoma and one epidermoid carcinoma with adenocarcinomatous components; the third, an oat cell variety, was too large to determine if peripheral or central in origin. It is concluded that the atypical epithelial changes observed in our cases, as well as those described in the literature, may progress to invasive malignancy. The present cases and a review of recorded cases of diffuse interstitial pulmonary fibrosis suggests that persons with this entity are prone to the development of lung cancer.

ESTIMATION OF TISSUE ELASTICITY OF THE LUNG.

Theoretical work-volume curves for liquid-filled lungs were constructed based on an assumed geometric form and deformation of the terminal air spaces and on the characteristics of single fibers of elastic tissue. These curves were compared with those measured in rats and with one taken from the journal literature in the case of a human lung. The form of the measured curves fitted the theoretical curves. The assumptions necessary were considered in detail. In both species more elastic tissue has been found present in the lung than would be expected theoretically. The action of additional restraining elements was thought necessary at high volume. pulmonary pressure-volume curves; pulmonary work-volume curves; lung volume and elastic tissue mass; pulmonary elastic tissue; tissue elasticity; pulmonary mechanics Submitted on April 22, 1963

The Interrelationships of Pulmonary Surface Tension, Ventilation, and Circulation.

s1 April 1962The Interrelationships of Pulmonary Surface Tension, Ventilation, and Circulation.J. A. Clements, M.D.J. A. Clements, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-695_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince it was demonstrated that normal mammalian lungs maintain favorable surface propties by secreting in the terminal air spaces lipoprotein rich in phospholipid, interest has grown in the normal role of such intrinsic surfactant and its possible alterations in pulmonary dysfunction. The presentation consists of four parts: [1] a brief review of experimental evidence proving that surfactant is present in normal lungs and leading to discussion of its effects on mechanical properties of lungs and on ventilation and of effects of exogenous surfactant on these properties, [2] current status of certain surface lesions of the alveolar structure which are thought... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, Calif. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 695-695KeywordsLesionsLipoproteinsLungsPhospholipids Issue Published: 1 April 1962 PDF downloadLoading ...

Hyaline Membrane Disease of Newborn Infants Its etiology and significance. Pulmonary hyaline membrane and congenital alveolar dysplasia*

Summary1) Hyaline membrane disease, as a pathological entity was studied histologically and biochemically. Histochemical tests routinely available, failed to reveal specific identifiable characteristics between hyaline membrane and other interalveolar foreign amorphous matter.2) Observation from our experimental results on rabbits and from autopsied materials of newborns and others, disclosed that hyaline membrane is a pattern of membranous alveolar lining and is derived from any source of inflammatory exudate, edema fluid and probably from aspirated amniotic sac content.3) Hyaline membrane and congenital alveolar dysplasia (Mac Mahon) are of distinctly different entities. Hyaline membrane is a foreign matter precipitated over the basement membranes of terminal air spaces, while the latter is a developmental defect of distal respiratory structures.

ADRENAL CORTEX EXTRACT IN PEDIATRICS&lt;subtitle&gt;Possible Effect on the Respiratory System of the Newborn&lt;/subtitle&gt;

THORN 1 considers and classifies acute adrenal insufficiency into three types. A fourth type of acute adrenal insufficiency, with congenital hypoplasia of adrenocortical tissue, occurs in the newborn infant. 2 The respiratory signs presented by a patient with this condition were definite. There was a disappearance of moist rales, cyanosis and dyspnea after replacement therapy. Because these manifestations recurred and increased in severity with the continued withdrawal of treatment with adrenal cortex extract, it appeared that adrenocortical hormone might exert a selective action on the cardiorespiratory system. This became more probable when a review of the records of several patients who suffered from a deficiency of this hormone revealed clinical and postmortem findings of pulmonary disease. 3 In addition, evidence has been presented that fatal hyalin-like membranes in the newborn might be caused by some injury to the epithelium and walls of terminal air spaces in pulmonary fields. 4 We

THE PATHOGENESIS OF THE "VERNIX MEMBRANE"

The clinical records of 79 stillborn and live-born infants were correlated with the postmortem findings in their lungs. Evidence of aspiration was found chiefly in the lungs of full term stillborn infants in the form of large numbers of blue-staining cornified epithelial cells together with large amounts of fat in the terminal air spaces. Hyaline-like membranes were found in the terminal air spaces in greatest numbers in the lungs of live-born premature infants in whom there was no history of any maternal complication of pregnancy or labor. It is suggested that the hyaline-like membranes may not be composed of aspirated vernix and amniotic sac contents but probably represent a reaction to an injury to the epithelium of the air spaces, especially the bronchioles and alveolar ducts. The nature of the etiologic agent remains doubtful, but the similarity of these membranes to those found in older individuals dying of pandemic influenza and with rheumatic pneumonitis suggests that intrauterine inflammatory reaction may be a factor. The relationship to congenital alveolar dysplasia has been discussed. It is suggested that the hyaline-like material is phagocytized by polymorphonuclear leukocytes and mononuclear cells. The presence of these phagocytes in the alveoli and bronchi in association with hyaline-like material is one of the chief forms of pneumonia in the newborn infant.