Fisiología respiratoria: fisiología del surfactante pulmonar / Physiology of pulmonary surfactant

El proceso de respiración y el intercambio gaseoso requiere la interacción de variadas fuerzas en los distintos tejidos y órganos involucrados. La tensión superficial a nivel alveolar provocaría colapso de dichas estructuras de no ser por las características del surfactante que lo recubre. Revisaremos en este articulo la fisiología involucrada en su estructura física, producción y efectos pulmonares.

The process of breathing and gas exchange requires the interaction of various forces in the different tissues and organs involved. The surface tension at the alveolus would cause collapse of these structures without of the surfactant that covers it. We will review in this article the physiology involved in its physical structure, production, and pulmonary effects.

Pulmonary surfactants and their role in pathophysiology of lung disorders.

Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.

Terapia com surfactante na síndrome do desconforto respiratório agudo: prós e contras / Surfactant therapy in acute respiratory distress syndrome: pros and cons

A síndrome do desconforto respiratório agudo (SDRA) acarreta disfunção quantitativa e qualitativa do sistema de surfactante pulmonar endógeno, levando à disfunção respiratória. Nesse contexto, a administração de surfactante pode vir a ser uma opção de terapêutica na SDRA, com importante impacto sobre a função pulmonar e a oxigenação. O presente artigo apresenta uma breve revisão acerca do potencial terapêutico do surfactante na SDRA. Para tal, foi realizada uma revisão sistemática da literatura, através das bases de dados MedLine, Scielo e Lilacs, onde foram incluídos artigos dos últimos anos, referentes ao assunto. Os artigos incluídos abordaram a terapêutica de reposição do surfactante em estudos experimentais e clínicos, assim como revisões sistemáticas sobre aspectos bioquímicos e fisiológicos do surfactante e da SDRA. Apesar de diversos estudos experimentais terem evidenciado efeitos benéficos com o uso do surfactante exógeno na SDRA, proporcionando melhora da função pulmonar, os trabalhos clínicos vêm apresentando resultados controversos. Entretanto, a administração de novos surfactantes exógenos tem apresentado resultados promissores. Concluindo, o uso do surfactante exógeno pode vir a fazer parte do tratamento dos pacientes portadores de SDRA.

Acute respiratory distress syndrome (ARDS) causes changes in pulmonary surfactant leading to respiratory dysfunction. In this context, the administration of surfactant may become a therapeutic option for ARDS with significant impact on lung function and oxygenation. This article presents a brief review regarding the potential of surfactant therapy in acute respiratorydistress syndrome. We performed a systematic review of the literature using the following databases: MedLine,SciELO and Lilacs. Experimental and clinical studies related to surfactant therapy in ARDS as well as systematic reviews of the biochemical and physiological aspects of surfactant were included in the present manuscript. Despite several experimental studies have shown beneficial effects with the use of surfactant in ARDS, leading to improvement in lung function, clinicalstudies have shown controversial results. However, the use of new surfactants has providing promising results. Therefore, use of surfactant can become part of ARDS patient treatment.

The importance of surfactant on the development of neonatal pulmonary diseases

Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.

O surfactante pulmonar é uma substância composta por um complexo lipoprotéico essencial para a função pulmonar normal. As proteínas do surfactante têm importante papel na estrutura, função e metabolismo do surfactante. São descritas quatro proteínas específicas denominadas surfactante pulmonar-A, surfactante pulmonar-B, surfactante pulmonar-C e surfactante pulmonar-D. Evidências clínicas, epidemiológicas e bioquímicas sugerem que a etiologia da síndrome do desconforto respiratório é multifatorial com um componente genético significativo. Existem na literatura algumas descrições sobre a presença de polimorfismos e mutações em genes dos componentes do surfactante, particularmente no gene da surfactante pulmonar-B, os quais parecem estar associados à síndrome do desconforto respiratório, síndrome da angustia respiratória aguda e proteinose alveolar congênita. Diferenças individuais relacionadas à síndrome do desconforto respiratórioe síndrome da angustia respiratória aguda e à resposta dos pacientes ao tratamento podem refletir diversidade fenotípica, devido, parcialmente, à variação genética. O estudo das diferenças entre as variantes alélicas dos genes das proteínas do surfactante pode ajudar na compreensão das variabilidades individuais na susceptibilidade ao desenvolvimento de várias doenças pulmonares. A determinação de quais polimorfismos e mutações são, de fato, importantes na patogênese das doenças relacionadas à disfunção das proteínas do surfactante e a possibilidade da realização da genotipagem em indivíduos de alto risco constitui um novo campo de pesquisa, que pode permitir, futuramente, um aconselhamento genético mais efetivo, resultando no desenvolvimento de estratégias profiláticas e terapêuticas que representem um impacto real no manejo dos recém-nascidos portadores da síndrome do desconforto respiratório e outras patologias pulmonares.

El surfactante pulmonar en neonatología / Pulmonary surfactants in neonatology

This is an admission thesis to the Panamenian Academy of Medicine and Surgery. We reviewed the use of the pulmonary surfactant in neonatology, the history, biochemical and biophysical properties; the metabolism and commercially available preparations were also analyzed. We presented the international clinical experience and our own in Panama

In vitro effect of meconium on the physical surface properties and morphology of exogenous pulmonary surfactant

The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.

Variación de los fosfolípidos, colesterol y triglicéridos en el suero con el uso de surfactante en neonatos con enfermedad de membrana hialina / Variations in phospholipids, cholesterol and triglycerids with exogen surfactant application in neonates with hialine membrane disease

El objetivo de este estudio prospectivo fue analizar las variaciones séricas de los lípidos y su repercusión al aplicar surfactante endotraqueal. Se formaron dos grupos, el A de neonatos a los cuales se les puso surfactante natural de extracto de pulmón de bovino y el grupo B al cual se les puso solución fisiológica. Los criterios de inclusión para ambos grupos fueron: ser menores de 37 semanas, diagnóstico de enfermedad de membrana hialina, necesidad de ventilación mecánica. A los dos grupos se les determinó fosfolípidos, colesterol y triglicéridos séricos antes (basales) y 24 horas después de aplicado el surfactante y la solución fisiológica (controles). Al conformar el grupo A vs el B los resultados obtenidos fueron: no encontramos diferencia estadística en cuanto a peso (1340 ñ 341 vs 1320 ñ 377) y edad gestacional (34 ñ 2.3 vs 34.6 ñ 1.8), tampoco en sexo, vía de nacimiento, Apgar y trofismo. Al comparar los valores controles de ambos grupos encontramos un aumento en el grupo A para fosfolípidos y colesterol (P<0.01). Al confrontar los valores basales vs controles encontramos aumento en el grupo A para fosfolípidos y colesterol (P<0.001), en el grupo B hubo una disminución en el colesterol (P<0.05). Concluimos que el uso de surfactante natural de extracto de pulmón de bovino, produce un aumento de los fosfolípidos y colesterol en sangre, sin repercusión hemodinámica

Efeito da hiperdistensäo alveolar no surfactante pulmonar de ratos submetidos a restriçäo alimentar / Effect of alveolar hyperdistension on lung surfactant of starved rats

O objetivo deste trabalho é observar se as alteraçöes dos parâmetros de ventilaçäo, basicamente volume corrente, contribuem para a modificaçäo do surfactante pulmonar em situaçöes de restriçäo alimentar. Para tanto, foram utilizados ratos adultos Wistar, submetidos a quantidades diferentes da mesma dieta alimentar e a dois padröes de ventilaçäo mecânic, de forma que se trabalhou com quatro grupos experimentais: grupo NN (n=26) - ratos recebendo dieta total e submetidos a ventilaçäo mecânica convencional, intercalada por duas fases de hiperdistensäo alveolar, em que o volume foi duplicado e a frequência respiratória reduzida à metade; grupo RN (n=24) - ratos em restriçäo alimentar, durante sete dias, e submetidos a ventilaçäo mecânica convencional; grupo RH (n=21) - ratos em restriçäo alimentar e submetidos a ventilaçäo mecânica com hiperdistensäo alveolar. Procurou-se detectar alteraçöes na quantidade e qualidade do surfactante pulmonar, observando-se as trocas gasosas pulmonares, a curva pressäo-volume com insuflaçäo de ar e líquido, a quantidade de fosfolipídios totais recuperados na lavagem pulmonar e o estudo anatomapatológico dos pulmöes. Como näo foi evidenciada nenhuma alteraçäo significante ao se compararem os quatro grupos de animais em relaçäo aos diversos parâmetros coletados e analisados, concluiu-se que a hiperdistensäo alveolar pelo período de tempo instituído e a restriçäo alimentar nos moldes estabelecidos näo levaram a alteraçäo, nem na quantidade nem na qualidade, do surfactante pulmonar

Impacto económico del uso de surfactante pulmonar sintético para el tratamiento de la enfermedad de membrana hialina en recién nacidos prematuros

El uso de surfactante pulmonar para el manejo de la enfermedad de membrana hialina constituye uno de los mayores logros de la medicina neonatal en los últimos años. Diferentes estudios clínicos han demostrado ampliamente los beneficios del uso del surfactante en prematuros con membrana hialina. La efectividad de su uso está plenamente comprobada, y teniendo en cuenta que la meta que se busca con su uso es disminuir la incidencia de displasia broncopulmonar y la mortalidad generada por la enfermedad, consideramos que su utilización tiende a reducir los costos finales de tratamiento por disminución del tiempo de ventilación asistida y las complicaciones. Basados en lo anterior, quisimos conocer los costos finales de tratamiento generados, por la enfermedad de membrana hialina, en un grupo de pacientes de la ciudad de Bogotá, ya que dados los limitados recursos económicos y locativos que tenemos para la atención del recién nacido de alto riesgo es importante conocer que terapia brinda los mejores resultados a un costo menor en nuestro país. Nosotros realizamos un estudio de identificación de costos generados por la enfermedad, en un grupo de pacientes manejados con y sin surfactante pulmonar. Encontramos que la terapia con surfactante pulmonar disminuye el tiempo de ventilación asistida (67 hr vs 100 hr p=0.26) y la mortalidad (4.54 por ciento vs 13.6 por ciento p=0.57). El costo final de tratamiento fue menor en el grupo con surfactante (2ï455.000 vs 2ï813.000 pesos p>0.05). De acuerdo con nuestros resultados podemos concluir que el uso de surfactante pulmonar no incrementa los costos de manejo de la enfermedad de membrana hialina.

Papel compensador del inositol y de los triglicéridos sobre los efectos de la desnutrición en los fosfolípidos del surfactante del pulmón neonatal / Compensatory role of inositol and triglycerides on the effects of malnutrition in the lung surfacatant phospholipids of newborns

La desnutrición puede ser una causa o consecuencia de deficiencias ventilatorias en el pulmón perinatall. La desnutrición disminuye el metablosimo oxidativo del pulmón y los procesos anabólicos incluyendo la síntesisla secreción del surfactante. En el presente trabajo se analizan los cmbios inducidos por una dieta materna hipoprotéica e hipocalórica durante la gestación y la lactancia, en la composición química de las fracciones surfactante y residual, aisladas del pulmón de ratas recién nacidas. Se estudian también los efectos de la suplementación de la dieta materna durante la lactancia con inositol y los efectos de inyecciones intraperitoneal de triglicéridos a los recién nacidos

Effect of malnutrition on lung phospholopid, pressure-volume curve and arterial blood gases: experimental study in rats

In order to study the effects of chronic malnutrition on lung surfactant, adult male Wistar rats reciving a standard diet (SD) were comparaed to animals submitted to food restriction (FR). SD rats given food and water and libitum and FR rats were allowed half (10g) of their usual food comsumption and water ad libitum, for 28 days. the evaluation of the pulmonary surfactant included pressure-volume curve with air inflation, pH and artherial blood gas measurements with rats breathing room air and 100 percent oxygen and determination of phospholipids in the lung washouts. In the pressure-volume curve, the volumes retained at 5 and 10 cmH2O of transpulmonary pressure (Tpt) and the Tpt of 40 percent of total lung capacity (TLC) were not significantly different between the two groups, showing that food restriction did not increase the surface forces. the increase in TLC/lung wet weight ratio in the FR group, probably was secondary to decrease in the elastic recoil forces in the lungs. The PaO2 did not show any significant difference between the groups. The arterial blood pH and PCO2 were also similar in both, SD and FR groups. Total phospholipid content in the lung washouts related to be weight was not signifiantly different in SD as compared with FR rats. Therefore, in this malnutrition model of rats, no alterations in pulmonary surfactant could be shown

Influence of thyroid hormone on the phospholipid composition of lung tissue and surfactant of rats.

Thyroid hormone is an important regulator of lipid metabolism in vivo. The effect of thyroid hormone on the phospholipid composition of lung tissue and surfactant has been studied in hypothyroid and hyperthyroid rats in comparison with the control rats. Rats were made hyperthyroid by administering 1 mg of L-thyroxine/kg body weight for six days. Another group of rats was rendered hypothyroid by injecting 1 mci of Na I131 to each rat. Phosphatidyl choline, lysophosphatidyl choline, lysophosphatidyl ethanolamine, phosphatidyl ethanolamine, and sphingomyclin, were estimated by thin layer chromatography. A decrease in phospholipids in hypothyroid and an increase in the hyperthyroid rats was observed. This can be attributed to the altered thyroid activity.

Diesel automobile exhaust anad lung surfactant activity in an experimental study, in rats.

It has been observed that the lung surfactant activity decreased after exposure of the animals to diesel automobile exhaust. This decreased lung surfactant activity could be an important factor in the pathogenesis of pulmonary oedema and collapse seen in our experiments.