Fisiología respiratoria. Neumología de altura: saturación de oxígeno, edema pulmonar y pruebas de función pulmonar / Respiratory physiology - High -altitude pneumology: oxygen saturation, pulmonary edema and pulmonary function tests

En las alturas, sobre todo a 2500 metros sobre el nivel del mar, la cantidad absoluta de oxígeno va decreciendo y por lo tanto la cantidad disponible para el intercambio gaseoso disminuye, produciéndose una vasoconstricción hipóxica pulmonar (VHP). La VHP asociada a la hipoxia hipobárica de la altura produce un aumento de la presión pulmonar que es mayor en los lactantes y a mayores alturas. No hay valores únicos de saturación de oxígeno (SatO2) en la altura, porque ésta va disminuyendo según el mayor nivel de altura, aumenta con la edad, y la brecha entre la vigilia y sueño es grande (sobre todo en los primeros meses de vida). El 25% de los niños sanos que viven en altura tienen valores de SatO2 significativamente menores que el 75% restante. Los valores normales de los índices de apnea/hipopnea son distintos a los de nivel del mar. El edema pulmonar de las alturas es una patología frecuente, que se produce por un incremento desproporcionado en la VHP reflejando una hiperactividad del lecho vascular pulmonar ante la exposición aguda a la hipoxia hipobárica. Tiene cuatro fenotipos, es infrecuente en menores de 5 años y rara vez es mortal, la sospecha clínica y el manejo oportuno con oxigeno es la clave. Finalmente, en la altura los valores normales de la función pulmonar de la espirometría, oscilometría de impulso y capacidad de difusión son distintos que a nivel del mar.

At high altitude, especially > 2,500 meters above sea level, the absolute amount of oxygen decreases and therefore the amount available for gas exchange decreases, producing hypoxic pulmonary vasoconstriction (VHP). VHP associated with high-altitude hypobaric hypoxia produces an increase in pulmonary pressure that is greater in infants and at higher altitudes. There are no single values of oxygen saturation (SatO2) at altitude, because it decreases with the highest level of altitude, increases with age, and the gap between wakefulness and sleep is large (especially in the first months of life). Around 25% of healthy children living at altitude have SatO2 values significantly lower than the remaining 75%. The normal values of the apnea/hypopnea indices are different from those at sea level. High altitude pulmonary edema is a frequent pathology that is produced by a disproportionate increase in VHP reflecting hyperactivity of the pulmonary vascular bed in the face of acute exposure to hypobaric hypoxia, it has four phenotypes, it is uncommon in children under 5 years of age, and it is rarely fatal, the clinical suspicion and timely management with oxygen is the key. Finally, at high altitude, the normal values of lung function from spirometry, impulse oscillometry, and diffusing capacity are different from those at sea level.

Mal agudo de montaña: pasado, presente y futuro / Acute mountain sickness: past, present and future

Evidencias en textos históricos Chinos de los años 403 AC y de la Conquista Española en 1590, muestran de las condiciones singulares que afectaban tanto a hombres como a animales al ascender por sectores montañosos por sobre 4000 m., y que ahora reconocemos como mal agudo de montaña. Ya desde el siglo XIX, se ha reconocido que es la falta de oxígeno (hipoxia) el factor determinante de la respuesta aclimatatoria como de la desaclimatización a la hipoxia de altura. El objetivo de la actual revisión fue una puesta al día de definiciones, factores que inciden en una mayor incidencia de mal agudo de montaña, mecanismo fisiológico propuesto, el desarrollo de estrategias farmacológicas para la prevención y/o tratamiento y por último, se ha revisado respecto de las distintas estrategias que se han desarrollado para la evaluación de la susceptibilidad individual, conocido comúnmente como test de hipoxia.

Some Chinese historical text from 403 BC and the Spanish Conquest in 1590 indicates unique conditions that affected both men and animals when climbing mountainous areas over 4000 m. and that is currently known as Acute Mountain Sickness (MAM). Since the XIX century, the lack of oxygen (hypoxia), has been recognized as the main factor of the acclimatization and declimatization to the high altitude hypoxia. The aim of the current revision is an update of definitions, factors that contribute the Acute Mountain Sickness, the proposed physiological mechanism, the development of pharmacological strategies for the prevention and/or treatment, and finally, we reviewed the different strategies developed for the individual susceptibility assessment, generally known as hypoxia test.

Early Warning of Acute Altitude Sickness by Physiological Variables and Noninvasive Cardiovascular Indicators / 中国医学科学杂志(英文版)

Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude. Methods One hundred and six Han nationality male individuals were recruited to this research. Dynamic electrocardiogram, treadmill exercise test, echocardiography, routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively. Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness (AMS). Results Approximately 49.05% of the individuals developed AMS. The tricuspid annular plane systolic excursion (22.0±2.66 vs. 23.2±3.19 mm, t=1.998, P=0.048) was significantly lower in the AMS group at sea level, while count of eosinophil [(0.264±0.393)×109/L vs. (0.126±0.084)×109/L, t=-2.040, P=0.045], percentage of differences exceeding 50 ms between adjacent normal number of intervals (PNN50, 9.66%±5.40% vs. 6.98%±5.66%, t=-2.229, P=0.028) and heart rate variability triangle index (57.1±16.1 vs. 50.6±12.7, t=-2.271, P=0.025) were significantly higher. After acute exposure to high altitude, C-reactive protein (0.098±0.103 vs. 0.062±0.045 g/L, t=-2.132, P=0.037), aspartate aminotransferase (19.7±6.72 vs. 17.3±3.95 U/L, t=-2.231, P=0.028) and creatinine (85.1±12.9 vs. 77.7±11.2 mmol/L, t=-3.162, P=0.002) were significantly higher in the AMS group, while alkaline phosphatase (71.7±18.2 vs. 80.6±20.2 U/L, t=2.389, P=0.019), standard deviation of normal-to-normal RR intervals (126.5±35.9 vs. 143.3±36.4 ms, t=2.320, P=0.022), ejection time (276.9±50.8 vs. 313.8±48.9 ms, t=3.641, P=0.001) and heart rate variability triangle index (37.1±12.9 vs. 41.9±11.1, t=2.020, P=0.047) were significantly lower. Using the Lake Louise Score as the dependent variable, prediction equation were established to estimate AMS: Lake Louise Score=3.783+0.281×eosinophil-0.219×alkaline phosphatase+0.032×PNN50. Conclusions We elucidated the differences of physiological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level. We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.

Physiological Variables Associated with the Development of Acute Mountain Sickness / 中国医学科学杂志(英文版)

Objective To identify the physiological variables associated with the development of acute mountain sickness (AMS). Methods Eighty four young Chinese men residing at low altitude were taken to an altitude of 4000 m within 40 hours. At sea level and at high altitude, we measured the heart rate, blood pressure, and peripheral oxygen saturation (SpO2) respectively. We also collect blood samples from each participants before and after the altitude elevation. The blood routine and biochemical examinations were performed for all blood samples. The revised Lake Louise Criteria was adopted to diagnose AMS after the subjects arrived at the target high altitude. The association between the presence of AMS and subjects' physiological variables were analysed statistically. Results Of 84 participants, 34 (40.5%) developed AMS. Compared with non AMS group, in the AMS group, the percentage of neutrophils was significantly higher (64.5%±11.2% vs. 58.1%±8.8%, P =0.014), while the level of SpO2 was significantly lower (79.4%±5.4% vs. 82.7%±5.6, P=0.008). Binary logistic regression analyses emphasized the association of neutrophils (OR: 1.06, 95% CI: 1.01-1.12, P=0.034) and SpO2 level (OR: 0.87, 95% CI : 0.79-0.95, P=0.004) with the development of AMS. Conclusion The ability to sustain SpO2 after altitude elevation and the increase of neutrophils were associated with the development of AMS in young males.

Hipertensión y edema pulmonar de altura: Rol de la disfunción endotelial y de la programación fetal / Pulmonary hypertensión and lung edema at high altitude: Role of endothelial dysfunction and fetal programming

La altura constituye un fascinante laboratorio natural para la investigación médica. Si bien al principio el objetivo de la investigación en la altura fue la comprensión de los mecanismos de adaptación del organismo a la hipoxia y la búsqueda de tratamientos para las enfermedades relacionadas con la altura, durante la última década el alcance de esta investigación se ha ampliado considerablemente. Dos importantes observaciones han generado las bases para el crecimiento del alcance científico de la investigación en la altura. Primero, el hecho de que el edema pulmonar agudo de la altura constituye un modelo único para estudiar los mecanismos fundamentales de la hipertensión pulmonar y el edema pulmonar en humanos. Segundo, que la hipoxia ambiental asociada con la exposición a la altura facilita la detección de disfunción vascular pulmonar y sistémica en un estadio precoz. Aquí revisaremos los estudios que, capitalizando estas observaciones, han llevado a la descripción de nuevos mecanismos subyacentes del edema pulmonar y de la hipertensión pulmonar, y a la primera demostración directa de la existencia de una programación fetal sobre la disfunción vascular en humanos.

High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.

Effects of altitude on anthropometric and physiological patterns in Aymara and non-Aymara population between 18 and 65 years in the province of Parinacota Chile (3.700 masl) / Efectos de la altura sobre patrones antropométricos y fisiológicos en población Aymará y no Aymará entre 18 y 65 años de la provincia de Parinacota, Chile (3.700 msnm)

The aim of the study was to compare anthropometric and physiological patterns in a sample of 522 Aymara and non-Aymara individuals from Parinacota, Chile (3.700m). After signing voluntary informed consent forms, the residents were separated in two age groups. Groups A: 18 to 35 years, and Group B: 36 to 65 years, by sex and Aymara and non-Aymara ethnicity. The results of this study determined that anthropometric anteroposterior diameter (DAP) are higher in Aymara population. Biacromial diameter (DBA) is significantly lower in the Aymara population. Aymara males between 18 and 35 years are smaller than non-Aymara males. Aymara women had significantly lower heart rates. The respiratory rate is significantly lower in Aymara males and females from 18 to 35 years. Partial oxygen saturation (SaO2) is higher in Aymara women, compared with non-Aymara women. The body mass index (BMI) did not differ within each group according to age, however, in comparison between groups, older individuals independent of sex and ethnicity have index of overweight and obesity. In forced vital capacity (FVC), there is no difference in ages however, while comparing between ages, older populations independent of sex and ethnicity presented significant decreases in this parameter. This may reflect mechanisms of adaptation to the high altitude of Aymara native populations living in the Andes.

El objetivo de este estudio fue comparar patrones antropométricos y fisiológicos en una muestra de 522 individuos aymará y no aymará de la Provincia de Parinacota (3.700 msnm). Luego de la firma del consentimiento informado por los residentes se procedió a separar a los individuos en dos grupos etáreos: población de 18 a 35 años y de 36 a 65 años, según sexo y etnia aymará y no aymará. Los resultados de este estudio determinan que los patrones antropométricos de diámetro antero posterior del tórax son mayores en la población aymará. El diámetro biacromial, es significativamente menor en la población aymará. Los varones aymará de entre 18 a 35 años son de menor tamaño que los varones no aymará. Las mujeres aymará presentan una disminución significativa de la frecuencia cardiaca. La frecuencia respiratoria es significativamente menor en damas y varones aymará de 18 a 35 años. La saturación parcial del oxígeno es mayor en las damas aymará, respecto a mujeres no aymará. El índice de masa corporal no presenta diferencia dentro de cada grupo según edades, pero al comparar entre los grupos, los individuos de mayor edad independiente del sexo y la etnia presentan índice de sobrepeso y obesidad. La capacidad vital forzada, no presenta diferencias dentro de las edades, sin embargo al comparar entre las edades, las poblaciones de mayor edad independiente de la etnia y el sexo presentan disminuciones significativas de este parámetro. Esto posiblemente reflejaría mecanismos de adaptación a la altura de las poblaciones nativas aymará, que viven en los Andes.

Edema pulmonar de altura: Modelo de estudio de la fisiopatología del edema pulmonar y de la hipertensión pulmonar hipóxica en humanos / High altitude pulmonary edema. An experiment of Nature to study the underlying mechanisms of hypoxic pulmonary hypertension and pulmonary edema in humans

La altura, fascinante laboratorio natural de investigación médica, provee resultados con importantes implicancias para la comprensión de enfermedades que afectan a millones de personas que viven en ella, asi como para el tratamiento de enfermedades ligadas a la hipoxemia en pacientes que viven en baja altitud. El edema pulmonar de altura (EPA) es una entidad que pone en peligro la vida y que ocurre en sujetos predispuestos pero sanos. Esto permite estudiar los mecanismos subyacentes del edema pulmonar en humanos, sin la presencia de factores que presten a la confusión como enfermedades concomitantes. El EPA resulta de la conjunción de dos defectos mayores: acumulación de líquido en el espacio alveolar debido a una hipertensión pulmonar hipóxica exagerada, y alteración en la eliminación del mismo por un defecto en el transporte transepitelial alveolar de sodio. En esta revisión, describimos brevemente las características clínicas y revisaremos este novedoso concepto. Proveemos evidencia experimental de como la síntesis alterada de óxido nítrico y/o la disminución de su biodisponibilidad representan el defecto central que predispone a la vasoconstricción pulmonar hipóxica exagerada y a la acumulación de líquido en el espacio alveolar. Mostramos que la hipertensión pulmonar hipóxica exagerada, per se, no es suficiente para producir un EPA, y que una alteración en la eliminación del fluido del espacio alveolar representa un segundo mecanismo fisiopatológico importante. Finalmente, describimos cómo los nuevos aportes obtenidos de los estudios del EPA pueden ser trasladados al manejo de otros estados patológicos ligados a la hipoxemia.

High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, it has become clear that the results of high-altitude research may have important implications not only for the understanding of diseases in the millions of people living permanently at high altitude, but also for the treatment of hypoxemia-related disease states in patients living at low altitude. High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed, but otherwise healthy subjects, and, therefore, allows to study underlying mechanisms of pulmonary edema in humans, in the absence of confounding factors. Over the past decade, evidence has accumulated that HAPE results from the conjunction of two major defects, augmented alveolar fluid flooding resulting from exaggerated hypoxic pulmonary hypertension, and impaired alveolar fluid clearance related to defective respiratory transepithelial sodium transport. Here, after a brief presentation of the clinical features of HAPE, we review this novel concept. We provide experimental evidence for the novel concept that impaired pulmonary endothelial and epithelial nitric oxide synthesis and/or bioavailability may represent the central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and alveolar fluid flooding. We demonstrate that exaggerated pulmonary hypertension, while possibly a condition sine qua non, may not be sufficient to cause HAPE, and how defective alveolar fluid clearance may represent a second important pathogenic mechanism. Finally, we outline how this insight gained from studies in HAPE may be translated into the management of hypoxemia related disease states in general.

Effect of hypobaric hypoxia on visual evoked potential at high altitude.

The effect of hypobaric hypoxia on visual evoked potential (VEP) was studied in 27 male volunteers at sea level (SL), during the 1st and 3rd weeks of their stay at high altitude (HA) of 3,500 m and in the 1st week of their return to the sea level (RSL). Exposure to high altitude (HA) led to significant changes in VEP. The N1 wave latency of both right and left eye was significantly increased (P<0.05) during 3rd week of stay at the altitude which persisted even after the return to the sea level. The latency of P1 wave of both right and left eye was higher in 3rd week at high altitude but not significant statistically. But the delay in P1 latency persisted in 1st week of their return to sea level which was significant (p<0.05) statistically as compared to sea level. The latency of N2 wave was significantly decreased (P<0.05) during the 1st week of stay at HA and returned back to basal value in the 3rd week of stay at HA in both right and left eye. However, the changes observed in NPN complex in terms of wave latencies were within the physiological limits. The amplitude of wave N1-P1 of both the right and left eye did not show any change. The changes observed reflect the process of acclimatisation to 3500m high altitude.

Transporte aéreo de pacientes críticos: fisiología del transporte en altura / Air transportation of critical patients: physiology of altitude transportation

Se presentan aquí el cuando y el cómo deben ser transportados por vía aérea los pacientes que presentan diversas patalogías, especialmente aquellos que se encuentran en condiciones críticas.Se analizan las medidas preventivas y terapéuticas a considerar, incluyendo los efectos que puede tener la altura sobre las acciones del médico que acompaña o autoriza el traslado, además de las regulaciones internacionales, impuestas por la autoridades de la aviación y las líneas aéreas, que deben ser cumplidas para que un paciente agudo, o un pasajero portador de patología crónica, puedan viajar en avión

Effect of sojourn at altitude of 3,500 m on auditory evoked potential in man.

Auditory evoked potentials were studied on 27 male subjects to evaluate the effect of sojourn at high altitude (HA). They were initially studied at Delhi (260 m) for their auditory evoked potentials and were then flown to an altitude of 3,500 m. During their stay at HA the same parameter was tested twice, once on the second day of arrival at HA and another on 21st day of stay. Then they were flown back to sea level (SL) and were retested on the third day of return. The results showed a significant delay in the peak latency of wave I of both the right and left ears on the second day of arrival at HA with a persistent delay in wave V even after 3 days of return to SL. The results suggest that HA stress caused a delay in sensory conduction at the cochlear level during the first week of induction, which was normalised during further stay.

Effect of fiberoptic bronchoscopy on arterial blood gases and cardiac rhythm at a moderate altitude of 2250 meters.

OBJECTIVES: To study the effects of fiberoptic bronchoscopy (FOB) at an altitude of 2250 m on arterial blood gases (ABG) and cardiac rhythm abnormality. METHODS: Fifty consecutive patients undergoing fiberoptic bronchoscopy were evaluated for the arterial blood gases and cardiac rhythm changes at Shimla (a moderate altitude of 2250 m), where there is a state of ambient hypoxia. RESULTS: The changes were noted in five stages ranging from the levels before the procedure till 15 minutes after the completion of the procedure. The mean fall in PaO2 levels in this study was 8 +/- 2.45 mm Hg and the fall was maximum at the end of procedure. Both smokers and nonsmokers showed a significant fall but the fall was more severe in smokers. The mean fall in SaO2 in this study was 3%. The increase in heart rate and blood pressure during FOB was significant as compared to baseline levels. There was no significant change in PH, PaCO2, HCO3. The commonest rhythm abnormality noted was sinus tachycardia which was well tolerated. No major cardiac arrhythmia was noted. It was further seen that the duration of the procedure and type of special procedure undertaken did not effect the levels significantly. Cyanosis was the commonest complication encountered (36%) and was seen more frequently in smokers and those with age more than 40 years. It was observed during the induction of bronchoscope and also during the further negotiation of the bronchoscope into the smaller branches of bronchial tree. CONCLUSION: The changes in ABG and cardiac rhythm are comparable to the studies at sea level except the increased incidence of cyanosis.

Cambios fisiológicos durante la exposición aguda a la altura / Physiological changes during the acute exposition at high altitude

A continuación detallamos una serie de estudios realizados en el Perú, principalmente en el Instituto de Investigaciones de la Altura, y en el Instituto de Biología Andina, así como aquellos desarrollados en el extranjero sobre el efecto de la exposición aguda a la altura sobre las funciones del organismo, particularmente los hormonales y metabólicos, los hematológicos, cardiovasculares, y respiratorios.

Mal de montaña agudo: prevalencia y sus características / Acute altitude sickness: prevalence and characteristics

La presente revisión presenta datos sobre la prevalencia de mal de montaña agudo (MMA), y sus características. A 3400m de altura, la prevalencia es de 41.2 por ciento. La prevalencia aumenta conforme se incrementa la altitud de exposición. Treinta y cinco por ciento desarrollan síntomas dentro de las seis horas de exposición a una altura de 3400m. La saturación arterial de oxígeno al arribo a la altura fue mayor en aquellos sujetos que tiene síntomas de MMA dentro de las 6 horas de exposición a la altura se observan una caída significativamente de la saturación arterial de oxígeno en aquellos varones que hacen MMA que en aquellos que no hacen MMA. La prevalencia de MMA desaparece a las 96 horas de exposición a la altura. La presentación de MMA no predice una baja performance física en la altura.

Mal de montaña agudo: mecanismos fisiopatológicos / Acute altitude sickness: physiopathological mechanisms

Se desarrollan las bases fisiólogicas de la aclimatación a la hipoxia en función de las modificaciones que se observan en los sistemas respiratorios, y cardiovascular, así como en el transporte de oxígeno en la sangre. Se presentan las etapas de aclimatación a la altura en relación a la sintomatología y a los cambios fisiológicos que ocurren a lo largo de la aclimatación a la hipoxia aguda. Se describen las enfermedades provocadas por la exposición aguda a la altura (mal de montaña agudo -MMA- Edema Pulmonar de altura -EPA-, Edema Cerebral de altura -ECA-), así como los mecanismos involucrados y las consecuencias de la aparición de las mismas. Se postula que la superposición de hallazgos en las enfermedades mencionadas impide definir los límites clínico exactos de estas condiciones patológicas con claridad.