Abstract People living at sea level have poor tolerance to hypoxia. In striking contrast, humans experiencing hypoxia at high altitude live very well. How is it possible for man to tolerate extreme hypoxia at high altitude? In this article we propose a hypothesis that potentially explains the tolerance to hypoxia at high altitude. Close examination of values of hemoglobin and PaCO2 for an altitude of 3510 m demonstrate that an increase in hemoglobin (Hb) and a decrease in arterial carbon dioxide tension (PaCO2) are two essential changes that occur on high altitude exposure. We propose a formula : tolerance to hypoxia= Hb/PaCO2 * 3.01. We present evidence that the relationship between Hb and PaCO2 explains the tolerance to hypoxia at high altitude. Full article PDF citation: Gustavo R. Zubieta-Calleja, Gustavo Ardaya, Natalia Zubieta-De Urioste, Poul-Erik Paulev and Gustavo Zubieta-Castillo, http://altitudeclinic.com/blog/2013/04/tolerance-to-hypoxia/, April 10, 2013. Formula originally published at: http://altitudeclinic.com/blog/2012/08/the-tolerance-to-hypoxia-formula/
This is being presented for the first time at the Leh Hypoxia Symposium between Aug 3-5, 2012 and the Global Hypoxia Summit and 4th International conference on Chronic Hypoxia, held in New Dehli India between Aug 7-9, 2012.
Copyright by Gustavo Zubieta-Calleja – IPPA – La Paz, Bolivia
Clickee en la imagen para agrandar.
Gustavo Zubieta-Castillo y Gustavo Zubieta-Calleja
Publicado en la Revista Americana de Medicina Respiratoria 2011; 1: 5
Torricelli, Montgolfier y Pascal, podemos decir, fueron los que sentaron los principios científicos básicos para los estudios de la altura. Primero tenía que conocerse físicamente qué era la altura, había que cuantificarla y determinar que es exponencial. Esto dio lugar a los estudios del efecto de la menor presión parcial del oxigeno, conocido como hipoxia, sobre la función respiratoria y circulatoria. La atmósfera y el aire que rodea al planeta y el agua de los océanos contienen y están formados por los mismos elementos: oxígeno, hidrógeno y nitrógeno. Gracias a Torricelli tenemos el concepto científico de que la atmósfera tiene peso, utilizando primero el barómetro de agua, donde el peso es igual a 10 metros de altura (= 1 atmósfera), reemplazando luego por el mercurio que corresponde a 760 mmHg (= 1 atmósfera). Además, el peso de la atmósfera disminuye exponencialmente con la altura y alcanza los 20,000 m aproximadamente. En 1646 Torricelli y Pascal definen lo que hoy conocemos como la atmósfera. En la actualidad, un gran número de científicos se dedican al estudio de la altura. Uno de ellos es Peter Wagner, quien tiene amplia experiencia como fisiólogo del intercambio gaseoso. El articulo sobre el trabajo de Charles Houston en Operación Everest II presentado en esta edición de la Revista Americana de Medicina Respiratoria es muy interesante como referencia. Él estudió las respuestas fisiológicas de varios sujetos expuestos en una cámara hipobárica a nivel de la cima del Monte Everest. Cuando vino al 1er Congreso Mundial de Medicina y Fisiología de la Altura en 1994 en La Paz, Bolivia, Charles Houston, comentó que esa experiencia le había costado “blood, sweat and tears”; sangre, sudor y lagrimas. Esto debido a la complejidad de dicho estudio y a las dificultades en las relaciones humanas. Cuando entró a nuestro laboratorio de función respiratoria en la ciudad de La Paz, a 3510 m sobre el nivel del mar, al ver nuestra cámara Hiperoxica/Hipoxica de Adaptación a la Altura, exclamó “Oh, Barcroft’s glass chamber!”. Le hizo recordar la cámara de vidrio de Barcroft, donde estudió los gases en sangre arterial, denudándose la arteria radial para observar los cambios de concentración de oxígeno. Terminado el experimento se ligó la arteria. Nosotros utilizamos los valores de la presión arterial de oxígeno en relación a la altura para adaptarlos a los pacientes que sufren el mal de montaña crónico en la ciudad de La Paz. En éstos los niveles de oxígeno son comparables a los detectados en el estudio de Charles Houston en la “cima del Everest”. Esto nos indujo, entre otras observaciones, a plantear la hipótesis de que el hombre puede adaptarse a vivir en la extrema hipoxia de la cima del Everest y desarrollamos la formula: Adaptación = tiempo/altura. Naturalmente, esta idea no es aceptada por los que opinan que el hombre sólo puede vivir hasta los 5000 m, debido a que existen asentamientos humanos en minas a esas alturas. La capacidad de tolerancia a la altura es limitada por la hipoxia, el frío, la capacidad de adaptación, falta de alimentación adecuada y tiempo de adaptación insuficiente. Bibliografía - Zubieta-Castillo G, Zubieta-Calleja GR, Zubieta-Calleja L, Zubieta-Calleja N. Adaptation to life at the altitude of the summit of Mt. Everest. Fiziol Jornal 2003; 3: 110-7.
articulo original: http://www.ramr.org.ar/archivos/numero/ano_11_1_mzo_2011/mere1_5.pdf
Prof. Gustavo Zubieta-Castillo performed isolated dog heart perfusion in order to study heart function at high altitude. He then observed that the hearts of high altitude residents were more tolerant to hypoxia than those at sea level, around 1961. This is considered one of the first observations with this concept. Ever since and gradually it has been further studied and applied practically with distinguished colleagues such as Dr. Emilio Marticorena from Peru that showed that high altitude cardiac rehabilitation is faster at high altitude. Frantisek Kolar from the Czech Academy of Sciences Institute, has performed extraordinary advance in research of hearts in rats exposed to hypoxia, further advancing in this concept. We have heard that Alberto Hurtado from Peru had similar ideas. Here is the Newspaper “Ultima Hora” publication back in 1964:
Forever: “Loss of Adaptation” does not exist!
Prof. Dr. Gustavo Zubieta-Castillo (Sr)
Honorary Director Español (mas abajo)
Instituto Pulmonar y Patología de la Altura IPPA
La Paz, Bolivia
Chronic Mountain Sickness (CMS) is a term that does not explain the ethiopathogenesis of the disease in response to the effect of chronic hypoxia. There is no CMS, but rather pulmonary (mainly), cardiac, carotid, kidney, hematological or genetic disease. All these associated to an increase on the hematocrit or what is now known as polyerythrocythemia.
CMS, was described by Carlos Monge Medrano close to 90 years ago, He was unable to find an explanation for the signs and symptoms and chose to use the term “LOSS OF ADAPTATION”. This was originally accepted, but today it can be appreciated as lacking significance. And should stop being used.
Undoubtedly, CMS is a chronic hypoxic process resulting in an increase of hemoglobin, due to pulmonary lesions (fundamentally), that alter the pulmonary function, thereby reducing the oxihemoglobin saturation and stimulating the increase of red blood cells. This, essentially, in pulmonary lesions that are sequelae of diverse lung disease giving rise to intra-pulmonary shunts or uneven ventilation-perfusion. The term “LOSS OF ADAPTATION”, is even semantically inadequate, because in nature, living beings tend to adapt to different environments and circumstances. These could be: going to high altitude, temperature changes, solar radiation, UV radiation, diet changes, etc, etc . Consequently, to insist in contemporary medicine on the use of “LOSS OF ADAPTATION”, is not only a mistake, but rather foolishness!
On the other hand, if one is convinced as to the cause of a disease, where other scientists are in disagreement, it is futile to incur in the use of insults. In the International Chronic Mountain Sickness Consensus Group, you Fabiola Leon-Velarde, recurred to them in your e-mail on January 09, 2005 with the expression as follows:
“Third, we have agreed in Xining that any member of the group who have had a different opinion in any point, should send a letter to the Journal informing about the discrepancy. Of course, if any member of the group do not agreed at all with the Consensus, he should ask that his name is retired from the list of names, otherwise his letter will appear a little bit esquizofrenic.”
Please note that you misspelled the word… “schizophrenia”. This is what happens when one is not a medical doctor and doesn’t have medical knowledge. You live in Lima, at sea level,and your brief visits to high altitude, give you no authority or experience on disease at high altitude. Through your attitude, you are confusing world researchers. This has to be said for the sake of truth. Your knowledge should be restricted to the spectrum provided by your occupations instead of persisting on the use of “loss of adaptation” in regards to CMS. To have written a book entitled “Desadaptation a las grandes Alturas” (Loss of adaptation to high altitude) is to insist and confirm that you hardly understand the basic concepts of nature. A grave mistake, with no return.
In reference to this article please read “Consensus statement on chronic and subacute high altitude diseases” (1) . where we participated as a minority with an opposite standing versus “Loss of Adaptation”. We stated our concepts in regards to CMS within the aforementioned group (comments are available, on-line (3,4).) In that group, there were many prestigious scientists, from around the globe, but most of them lacked knowledge about diseases at high altitude.
We urge the reader not to misinterpret us. We are not offended by the insult, and quite the contrary we laughed upon reading it as anecdotal. What we are doing here is setting things straight, for the sake of science. The term “loss of adaptation” is inadmissible as it does not explain an ethiopathogenesis.
We are so convinced, based on our fifty years of high altitude research and experience, that living beings not only adapt to life at 5000m, as it is well known, but rather even to 8842m at the summit of Monte Everest. There can be no doubt.
Similarly, pulmonary and cardiac patients in chronic hypoxic environments at high altitude, also adapt, hand in hand with their disease. Polyerythrocythemia, is one of the resulting hematologic mechanisms that allows for an increase of the oxygen content.
You, on purpose, as you have done before, exclude us from participating in the THE VIII WORLD CONGRESS ON HIGH ALTITUDE MEDICINE AND PHYSIOLOGY – CARLOS MONGE CASSINELLI. Congratulations for naming it after our dear friend Choclo.We remind you that we initiated these world congresses successfully, in Bolivia, back in 1994. We invited everyone dedicated to high altitude to attend, including yourself as you were Choclo’s collaborator.
We are now at our III CHRONIC HYPOXIA SYMPOSIUM in October 2010 in La Paz, Bolivia. You and everyone are invited to attend, with no restrictions, nor political interest groups, that often block the participation of some, that think different.
Throughout history, all living beings, go through evolution, in order to adapt to different environmental conditions. Even aging is an evolution, that goes to finish a vital cycle. It never goes in the reverse way. This concept of loss of adaptation is unacceptable.
Again, “The organic systems of human beings and all other species tend to adapt to any environmental change and circumstance within an optimal period of time, and never tend towards regression which would inevitably lead to death” (2)
La Paz, March 11, 2010
Para siempre: La “Desadaptación a la Altura”: No existe !
Prof. Dr. Gustavo Zubieta-Castillo (Sr)
Instituto Pulmonar y Patología de la Altura IPPA
La Paz, Bolivia
El Mal de Montaña Crónico (CMS), es un término inadecuado porque no explica la etiopatogenia de la enfermedad. Las enfermedades en la altura sufren el efecto de la hipoxia crónica. No existe el mal de montaña crónico sino las enfermedades pulmonares de diferente etiopatologia que van asociadas al aumento del hematocrito o polieritrocitemia.
Carlos Monge Medrano, describió admirablemente los síntomas y signos del Mal de Montaña Crónico. Al no encontrar una etiología adecuada, para esa época, utilizó el termino DESADAPTACION. Este término aceptado al principio, se puede comprobar que actualmente no tiene significación.
El síndrome de Mal de Montaña Crónico, se sabe actualmente, sin que pueda hacerse objeciones, es fundamentalmente, un proceso crónico hipóxico con un aumento del hematocrito. Esto debido a lesiones pulmonares que alteran la función respiratoria y que impiden la adecuada saturación de la sangre estimulando el aumento de los glóbulos rojos. Sobretodo es debido a secuelas de lesiones pulmonares de diversa etiología con shunt pulmonar y/o ventilación no uniforme. El termino desadaptación, es incluso semánticamente inadecuado porque en la naturaleza los seres biológicos tienden a la adaptación a diferentes medios y circunstancias. Como ser: cambio de altura, de temperatura, radiación solar, radiación UV, cambio de alimentación, etc, etc. De manera que insistir en la medicina contemporánea con el termino desadaptación, no solo es un error, sino una insensatez!
Por otra parte si uno tiene la convicción sobre las causas de alguna enfermedad, con la cual no están de acuerdo otros científicos, no es esto motivo, para que se recurra al insulto. La ecuanimidad esta en reconocer que uno puede equivocarse pero no tratar de imponer criterios recurriendo al insulto como lo esta haciendo Ud. Fabiola Leon Velarde.
Para referencia está la publicación “Consensus statement on chronic and subacute high altitude diseases”(1) donde participamos minoritariamente con una posición contraria a la Desadaptación.(3,4). Ese grupo de prestigiosos científicos de todo el mundo, tenian escaso conocimiento de las enfermedades en la altura.
Durante las reuniones previas en Jan09,2005, Ud. nos escribió (traducido al Español):
“Tercero, hemos acordado en Xining, que cualquier miembro del grupo que tuviera una opinión diferente, debería enviar una carta al Journal informando de esa discrepancia. Por supuesto, si algún miembro del grupo no esta de acuerdo con el Consenso, debe pedir que su nombre sea retirado de la lista de nombres, de otra manera su carta aparecería algo esquizofrénica. (esquizofrenic en la version en ingles)”
Ojo, en Inglés se escribe “schizophrenia”.
Su audacia no tiene limites, porque Ud. no es medico y por lo tanto no sabe medicina. Ud. vive en Lima, a nivel del mar, y sus visitas esporádicas a la altura no le dan ninguna autoridad ni experiencia y esta confundiendo a los investigadores presentando estos casos. Sus conocimientos deberían estar limitados al espectro que le permitan sus ocupaciones y no tratar de insistir de que el mal de montaña es debido a “desadaptacion”. Haber escrito un libro titulado “Desadaptación a las grandes alturas” es insistir y confirmar que no se entiende los conceptos básicos de la naturaleza. Error cometido irremediablemente.
No nos ofende, ni causa resentimiento que Ud. en esa oportunidad, nos llamó esquizofrenicos, y sentimos por el contrario que es motivo de buen humor y anecdotico. Lo que estamos haciendo es afirmar que el termino desadaptación es inadmisible porque no explica ni señala una etiopatologia.
Estamos tan convencidos que el ser biológico no solo se adapta a la vida a los 5000m, sino hasta los 8842m en la cima del Monte Everest. No cabe duda… De igual forma los enfermos pulmonares o cardiacos en el ambiente hipóxico de la altura, también se adaptan con su enfermedad, resultando la polieritrocitemia, un mecanismo para aumentar el contenido de oxígeno.
Ud. nos excluye intencionalmente del VIII Congreso Mundial de Medicina y Fisiología de la Altura, cuya serie, nosotros iniciamos exitosamente en Bolivia el año 1994, al que invitamos cordialmente a todos dedicados a la altura, incluyéndola a Ud. por ser la colaboradora de nuestro amigo Carlos Monge Casinelli. Nos alegramos que el VIII sea en honor a nuestro amigo Choclo.
Nosotros tenemos el III Simposio del Efecto de La Hipoxia Crónica en las Enfermedades en la Altura en Octubre 2010, al cual queda Ud. Cordialmente invitada, aquí en La Paz. Todos están invitados a participar, sin restricciones, ni grupillos de interés político común, como frecuentemente ocurre bloqueando intencionalmente la participación de algunos, que opinan diferente.
A través de la historia, todos los seres vivientes evolucionan, para adaptarse a diferentes condiciones ambientales. Incluso la edad es una forma de evolución, que se dirige a finalizar un ciclo. Nunca va en sentido contrario. Este concepto de Desadaptacion es inaceptable.
Nuevamente, “Los sistemas orgánicos de los seres humanos y de las otras especies tienden a la adaptación a cualquier cambio ambiental, dentro de un periodo óptimo de tiempo, y nunca tienden hacia la regresión que inevitablemente daría curso a la muerte”.(2)
La Paz, 11 de marzo de 2010
1) León-Velarde F, Maggiorini M, Reeves JT, Aldashev A, Asmus I, Bernardi L, Ge RL, Hackett P, Kobayashi T, Moore LG, Penaloza D, Richalet JP, Roach R, Wu T, Vargas E, Zubieta-Castillo G, Zubieta-Calleja G.
Consensus statement on chronic and subacute high altitude diseases.
High Alt Med Biol. 2005 Summer;6(2):147-57
Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia.
J Physiol Pharmacol. 2006 Sep;57 Suppl 4:431-42.
The following excerpts are from the E-mail discussion of the committee on chronic mountain sickness, prior to The 3rd World Congress on Mountain Medicine and High Altitude Physiology and The 18th Japanese Symposium on Mountain Medicine carried out in Matsumoto, Japan (May 20th – 24th, 1998). This is part 2/2
Respiratory studies in the Hyperoxic/Hypoxic Adaptation Chamber
Date: 31 Mar 1998 08:23:27 U From: “John Reeves” Subject: Re: CMS discussion To: “Gustavo Zubieta” Cc: “Ingrid Asmus” , “Linda Curran” , “Dr. Gerilli” , “GUSTAVO ZUBIETA, M.D. * IPPA *” , “Toshio Kobayashi” , “Fabiola Leon-Velarde” <firstname.lastname@example.org>, “Shigeru Masuyama” , “Prof. Mirrakhimov” , “Carlos Monge” , “Hideki Ohno” , “Lorna G. Moore”3/31/98 8:20 AM
Thank you so much for the thoughtful remarks. They are extremely useful for the purposeof initiating discussion. As a bystander who does not see CMS patients, but who is interested in consensus, I do see differences of opinion that could and should be laid out on the table for friendly discussion, where everyone benefits. Getting these diverse opinions in ahead of the meeting should make people aware of the differences, and allow them to think about the problems. I hope you agree. Final answers may not come from the meeting, but the process of discussion will have been initiated. I am trying to keep Wu informed by fax of these discussions, but am not sure the faxes are getting through. I have taken the liberty of sending your thoughtful comments around, as I believe they deserve wide distribution. I hope that is O.K.
Date: 3/30/98 4:05 PM To: John Reeves From: GUSTAVO ZUBIETA, M.D. * IPPA *
Here goes the homework requested by you, Lorna Moore and her colleagues. We feel troubled by the subject of scoring CMS. As you can read from our publications, we are confident that there is no “loss of adaptation of life at altitude”, but rather an adaptation of pulmonary, cardiac, renal or other disease to the hypoxia at high altitude. (And to tell you the truth, CMS patients do remarkably well, provided their basic disease is treated or looked after).
In general, patients with CMS are examined while attending a regular consultation. Most often, after suffering the disease during many years and only when they and their family become aware of the change in the color of the skin, particularly in the face. Also, when the consultation is for another kind of disease and the routine laboratory tests report increased polycythemia. At this time, the signs and symptoms can be present in different degrees and are prominent or more evident in THS. The score will only be valid for some patients with CMS and exclude others.
Gastrointestinal ulcers, are frequent findings. Gastro-intestinal bleeding, will change the score. The same happens with Gout. Several patients with CMS have increased uric acid, and some with evident signs of Gout by deposits in the ear helix. Gout can lead to well known pulmonary alterations. Similarly, hypertension is also present in some of them. This generally implies kidney disease. Finger clubbing is present in some, even when they are very young.
In broncho-pulmonary lesions of smokers, for example, there can be severe cyanosis, low saturation, increased polycythemia and pulmonary hypertension. If they stop smoking there is significant improvement. This is the same as at sea level, but in chronic hypoxia they reach lower saturation. Another example are some patients with asthma. This shows that CMS patients have a different etiopathogenesis. If all these examples are not included, are they going to be considered a different kind of disease? It does not seem so.
At altitude, “cyanotic pulmonary diseases and asymptomatic high altitude polycythemia” (as defined by Hultgren) are, in our experience, CMS, and the later approaches more exactly CMS present at moderate altitude. If you use a score, you have to be aware that it will apply for that moment only and it will most probably change even within the next few days. Also, great differences in scoring will be found, depending on the degree of compromise of lung or cardiac function, the type of disease, and of course the altitude. Why? Because patients that have CMS are subject to viral diseases, bronchitis, colds or even seasonal climate changes (we have a CMS patient with allergies). This we described as triple hypoxia syndrome (THS), an acute condition overimpossed on CMS (please see further down and the article in our Web page below). So, if the score pretends to be used to access the moments’ clinical state of the patient with CMS, that is fine. About scoring CMS: In the score used by Dr. Wu in CMS, the signs are present particularly in AMS and the triple hypoxia syndrome, that we also call “sorojche (AMS) in bed”. With the exception of hyperaemia in conjunctivae and mucosae, which are chronic. The scores 0, 1, 2 and 3 for none, mild, moderate and severe, seem adequate.
We think that everybody agrees that the disorder regresses on descent to sea level, in around one month. Patients who reascend to high altitude, and are exposed again to hypoxia, develop CMS once more. This is a mechanism of adaptation, to supply the necessary oxygen to the tissues. The patients from low lands with chronic pulmonary diseases commonly unnoticed at sea level, develop CMS at altitude. Are we going to consider these cases as a loss of adaptation?. Certainly not, it is hard to think in such a way. We agree that the most appropriate approach to score the disease, are the laboratory findings: hemoglobin or hematocrit and oxygen saturation, with or without carbon dioxide retention, depending of the severity of the case. For over 15 years now, we have been using a classification by number of red blood cells (“El mal de montaña crónico y los mineros”, published in the magazine of the Academia Nacional de Ciencias de Bolivia,1985;4:109-116), and it has proved to be a good guide in our medical practice. Originally, diagnosis was based on clinical examination, chest x- rays film and hemogram only, due to the lack of equipment. It is as follows: moderate 6.5 to 7.5 million RBC/mm3 severe 7.5 to 8.5 million RBC/mm3 grave > 8.5 million RBC/mm3 For 3600 m. of altitude only. We feel now that it would have been better to name them as mild, moderate and severe and to use the hematocrit or hemoglobin, which amount to the same thing.
———————- With respect to your 7th question, (a very good one, indeed); yes, there is an altitude at which everyone gets CMS. Please see the abstract “Pulmonary disease, CMS and gender differences at high altitude” that we plan to present as a poster. When the respiratory frequency and ventilatory capacity are unable to compensate the extreme hypoxia, the last resort for the human being is to develop severe pulmonary hypertension (right heart hypertrophy) and increase the number of the red cells. All permanent residents will be sick with CMS at 5500 m, for example at the mine of Chorolque located at 5562 m. Since not everyone has equal capacity of adaptation, the CMS will be more severe in some than in others, and still they will survive. Of course, in miserable conditions. In terms of genetic predisposition, CMS is most probable for some individuals, over 40 years old, who have a tendency to gain weight, but this is due to the predisposition to get sick from respiratory disorders. Also, about impairment of intelligence in these patients, and intelligence itself in chronic hypoxia, we drop the subject for the moment. It is important to mention that chest X-rays films as a test of diagnosis of CMS is mandatory, (and now CAT scan or NMR) as is the clinical history of pulmonary diseases, and the pulmonary function tests.
In summary, to answer the first question about Chronic Mountain Sickness, “What is it?”. We feel that the most simple description of CMS, is going to be the most adequate for the moment. In that respect we are closer to John Weil’s definition.
Our definition is: “CMS or Monge’s disease is found in residents at high altitude with some abnormal pulmonary function (increased shunt, impaired diffusion, uneven ventilation and/or hypoventilation), sequelae of diseases of diverse etiopathogenesis. These lead to a sustained (and variable) low oxygen saturation and cyanosis, giving rise to pulmonary hypertension and increased polycythemia as compensatory mechanisms of adaptation to the disease under chronic hypoxic conditions. The symptoms and signs are reversible by descent to sea level or by increasing the PIO2.”
Both of us (Gustavo Sr. and Jr.) discuss this subject profoundly and we only write down the subjects in which we are in full agreement. We are expectant of the discussion on the scoring system.
Gustavo Sr and Gustavo Jr.
Received: from Pmail on IPPA_0 by PegWaf v0.24 93.03.15 id 3382 ; Mon, 30 Mar 98 18:10:51 To: “John Reeves” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 30 Mar 98 18:10:51 Subject: CMS discussion Priority: normal X-mailer: Pegasus Mail v2.3 (R5). ————————————————————- Date: 10 Apr 1998 16:47:23 +0100 From: “John Reeves” Subject: FWD>Comments, please To: “Inder Anand” , “Ingrid Asmus” , “Peter Bartsch” , “Buddha Basnyat”
, “Linda Curran” , “Marlowe Eldridge” , “Bob Grover” , “Peter Hackett” <email@example.com>, “Toshio Kobayashi” , “Fabiola Leon-Velarde” <firstname.lastname@example.org>, “Shigeru Masuyama” , “Professor Mirrakhimov” , “Carlos Monge” , “Susan Niermeyer” , “Hideki Ohno” , “Akio Sakai” , “Tatiana Serebrovskaya” , “Peter Wagner” , “Gustavo Zubieta” , “Lorna G. Moore” Mail*Link(r) SMTP FWD>Comments, please
Very interesting and important comments from the Zubieta’s. Dr. Leon-Velarde and myself, the Zubieta’s and others would like to hear some comments on these points.
Date: 4/10/98 8:59 AM From: GUSTAVO ZUBIETA, M.D. * IPPA *
We completely agree with you, that we should be aware of the differences in opinions and also of the similarity in the approach to clarify some aspects in CMS. The paramount point of this forthcoming congress, I am sure (Gustavo Sr.), is that the assistants, while enjoying the friendship, try to find out some clues that will benefit thousands of people, who live, get sick and are treated at high altitude, all around the world. We are sure that everything you are doing is OK and please feel free and confident to make us notice any illogical digression of our part. Regarding the difficulty in making sure lungs are normal in CMS, because severe polycythemia itself alters gas exchange, Dr. West points out: “I would like to add a small point. Jack Reeves stated that ‘severe polycythemia itself alters [pulmonary] gas exchange’. I do not think this issue is settled. We induced severe normovolemic polycythemia in dogs (hematocrits up to 76%) and found no broadening of the distribution of ventilation perfusion ratios (J. Appl Physiol. 65:1686-1692, 1988). In the introduction to that article we reviewed the published studies on whether polycythemia impairs pulmonary gas exchange and no clear message emerged.” These interesting remarks, show us that many people think that polycythemia (of unknown etiopathogenesis), affects pulmonary function in CMS. According to Dr. West’s research, this would not be so.
Gustavo Sr, believes that those experiments resemble more what would happen in polycythemia Vera (Vaquez-Osler disease), where, according to the scarce bibliography, he has, there are no cardio-pulmonary alterations. If these experiments were repeated at high altitude, probably the results would be the same: No broadening of the distribution of ventilation-perfusion ratios. Some authors found that in polycythemia Vera, the pulmonary diffusing capacity was greater than in normals, attributed to increased hemoglobin concentrations (Journal of Clinical Investigation, Vol 4, NO. 7, 1963).
Polycythemia increases the total surface of red blood cells exposed to oxygen, which is another advantage. In Monge Medrano’s original paper, he thought that he found polycythemia Vera of high altitude (1928). Then he realized that it was not exactly the same so he changed his point of view to “loss of adaptation” and CMS (1937 & 1943).
The clinical description and observation of increased polycythemia was an important contribution to high altitude pathology, made 70 years ago. We look forward to the presentation by Carlos Monge and Fabiola Leon Velarde, our distinguished friends, on the history of how CMS was discovered . If the disease exists at high altitude, with the original description, Gustavo Sr. has not been able to see it in over 40 years of medical practice (and we were always looking for it). As you know there are thousands of people with increased polycythemia, in the Bolivian high plateau (abnormal), that can be easily diagnosed by simple observation in the streets, when there is the experience.
Some of the participants in the CMS discussion affirm that they have found people with CMS but with no anatomical or functional alterations. It seems to us that we are observing a different kind of pathology. By the way, we have neither seen one case of Polycythemia Vera. When one of us was in USA, nobody gave an adequate explanation about this last disease. The only thing I know for sure is that polycythemia vera is accompanied by leucocytosis, increased platelet count and can evolve to a very severe hematological disease.
As we previously pointed out, AFTER PROVING THAT THESE PEOPLE HAVE CARDIO-PULMONARY PATHOLOGY, ARE WE GOING TO EXCLUDE THEM FROM CMS OR MONGE’S DISEASE? For this reason, our point of view is that pulmonary diseases, that leave sequelae, give rise to low saturation and consequently CMS.
Lets suppose that 3 individuals, apparently normal, one 20 years old, and two 40 years old, move from the lower part of the city of La Paz, at 3000 m. They remain 3 months at 3500 m, and 3 months at 4100 m (in the city of El Alto, the highest part). The blood tests will show that the 20 years old and one of the 40 years old have their hemoglobin and hematocrit normal, for each altitude. The other has increased his hemoglobin to around 20 gm%. Can we say that this last one has “lost his adaptation”? and that the other two have adapted?. The last one has developed chronic mountain sickness. Do we call this: “adaptation” or “loss of adaptation” ?. This is not a hypothesis, it is a fact of common observation. Furthermore, if he has “lost his adaptation”, is he unable to live there any longer ?. Here, we are in the most critical point, in health problems. Should this man go to the lowlands, even though he feels well in the intellectual and physical conditions? When he becomes aware that he has CMS, it turns into a big economical and social problem. Of course, he will, from time to time, suffer from colds with headaches, lassitude, sleep disturbance and so on (as any healthy subject with a cold) that will be diagnosed by physicians as the CMS alteration, but in reality it is the triple hypoxia syndrome in CMS, that is transitory and treatable.
Since the participants are unable to go to discuss the cases in the different hospitals, clinics or laboratories, of each country, may we suggest that you ask each participant in the liberal discussion on CMS (if feasible), bring a color photograph of the patient, the clinical history, the laboratory findings, the cardio-pulmonary function tests or any additional data, to the meeting so that we can all see the differences and discuss them, in a friendly way. These results will show us more than a thousand words.
Gustavo Zubieta Sr. & Gustavo Zubieta Jr.
To: “John Reeves” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 10 Apr 98 10:12:34 Subject: CMS discussion Priority: normal X-mailer: Pegasus Mail v2.3 (R5). ———————————————————– Date: 20 Apr 1998 08:47:15 -0600 From: “Lorna G. Moore” Subject: Re: Lorna’s questions on “adaptation” To: “GUSTAVO ZUBIETA, M.D. * IPPA *” Cc: john.reeves@UCHSC.edu Reply to: RE>Lorna’s questions on “adaptation” Thank you for your interesting reply. If I interpret your remarks correctly, you are asking if the effects of CMS on life expectancy (mortality) are similiar to those of COPD at sea level (or at altitude). That might be an interesting way to get at the seeming confusion over the uniqueness of CMS as a high-altitude condition. Looking forward to seeing you in Japan!
Date: 4/19/98 7:28 PM To: Lorna G. Moore From: GUSTAVO ZUBIETA, M.D. * IPPA *
Dear Lorna: Your fundamental points regarding the term “adaptation”, stimulated and gave an electrifying boost to everyone’s thoughts. Thank you for letting us know the interesting definition of “adaptation” by Theodosious Dobzhansky. We had not heard it previously. First of all, I (Gustavo Sr) am compelled to explain the importance of the term “adaptation”, which concerns me very strongly.
Any term in medicine implies a concept (knowledge) of the diseases which will set the rules for prevention and treatment (CMS in this case). I include in CMS many kinds of pulmonary disease in chronic hypoxia. By associating CMS with the term “loss of adaptation”, attention has been focused only in the increase of the number of red blood cells. This, mislead many studies. With such a concept, many people with pulmonary disorders have been sent to the lowlands in order to reduce their hematocrit and they die very soon. Due to the hot, humid and oxygen rich environment (an optimum medium for bacteria) there is worsening of infectious diseases (tuberculosis, for example). Some remain living their life as anyone in the lowlands in any part of the world, with unnoticed mild respiratory or ventilatory impairment.
Another form of treatment was targeted to decrease the hematocrit, by using radioactive compounds (such as phosphorous) or cytolytic drugs (such as fenilhidrazine). Nowadays, the pharmaceutical market is full of “medicines” announcing that they can “reduce” the number of red blood cells. Phlebotomy has to be revised, in lieu of the advance of knowledge in hypoxia, but we will not deal with this subject in this letter.
In relation to impaired fertility: We don’t know of any specific studies, however it is a common observation that the fastest growing city (over 600,000 inhabitants) in Bolivia happens to be El Alto “the high plateau” (4100 m). There, according to a presentation we will give in Matsumoto, about 52% of the males and 28 % of females that receive medical attention in all diseases, have a hematocrit above 58 %. The people of the city of El Alto, reproduce even in the most disadvantageous conditions of poverty, lack of adequate housing, lack of hygiene and so on.
On the other hand, I (Gustavo Sr.) have studied sick miners of high altitude mining centers in Bolivia, who had increased polycythemia with pulmonary diseases and several of them had over 8 children. Many of the children died, because of bad sanitary, nutritional and infectious conditions in the mines. They only stopped having children when the women reached menopause. Incidentally, it is well known that human fetuses live in hypoxic conditions (and that they are polycythemic! ). That is probably why they don’t die, and can tolerate very long apneas and extreme hypoxia during delivery. At high altitude, it surprises us more.
By the way, breath-holding in CMS is one of our subjects of presentation in Matsumoto. In dealing with hypoxia, environmental factors should never be overlooked. For example, impotence that has to do with fertility, is not a common complaint at high altitude, as it happens in developed countries (paradoxical?) About life expectancy: There are no great differences between disease at sea level and at high altitude, in the course of life. Again, we know of no studies on life expectancy in respiratory disease at high altitude. For example, at sea level, chronic obstructive pulmonary disease (COPD) and emphysema affect 20-30 % of the adult population, with more than 60,000 deaths/year. The predominant age is over 40 and the predominant sex is male. This is strongly similar to our clinical observations here (except the death incidence per year, that is not quantified).
If patients with CMS, have reduced life expectancies, it will probably be due to a reduced life expectancy of chronic lung disease, just as at sea level. Depending on the severity of the cases, naturally. We have followed patients with CMS, for over 14 years, into their 80’s and we have never looked after one, the moment he died. No one has reported, up to date, an autopsy of CMS. Probably, because when the pathological alterations were discovered, they were classified as cardio-pulmonary disease. By the way, malnutrition, cor-pulmonale, hypercapnia and a pulse > 100 are all poor prognostic indicators in COPD at sea level. The same happens at high altitude.
Furthermore, cor-pulmonale in patients with CMS is probably an advanced and untreated consequence of respiratory disease. Increased polycythemia can’t be absent in many cases. At sea level, supplemental oxygen, has been shown to increase survival. This is conflictive for us. It would imply that there is a shorter life expectancy for high altitude residents, but that does not seem to be so. Ever since the use of penicillin, life expectancy has expanded also at high altitude. Previously, many people died of pneumonia in their forties. With better nutrition, improved health care, and more hygiene, we are seeing people, more and more, that live well into their nineties. We are not saying that altitude is the best place to live in, but just that we live here. We are aware of how easy it is to make a mistake or fall into speculation, but what you just read comes from our on-site experience, a lot of hypoxia and its interpretation….
Gustavo Sr. & Gustavo Jr.
—————— RFC822 Header Follows —————— Received: by defiance.uchsc.edu with ADMIN;19 Apr 1998 19:27:58 -0600 Received: from unbol.bo (unbol.bo [18.104.22.168]) by essex.UCHSC.edu (8.6.12/8.6.9) with SMTP id TAA01496 for ; Sun, 19 Apr 1998 19:31:26 -0600 Received: from oxygen.UUCP by unbol.bo (8.6.12/1.35) id VAA24235; Sun, 19 Apr 1998 21:26:59 +0400 Message-Id: <199804191726.VAA24235@unbol.bo> Received: from Pmail on IPPA_0 by PegWaf v0.24 93.03.15 id 8078 ; Sun, 19 Apr 98 20:37:23 To: “Lorna G. Moore” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 19 Apr 98 20:37:22 Subject: Lorna’s questions on “adaptation” CC: john.reeves@UCHSC.edu Priority: normal X-mailer: Pegasus Mail v2.3 (R5).
The following excerpts are from the E-mail discussion of the committee on chronic mountain sickness, prior to The 3rd World Congress on Mountain Medicine and High Altitude Physiology and The 18th Japanese Symposium on Mountain Medicine carried out in Matsumoto, Japan (May 20th – 24th, 1998). Part 1/2.
From: “GUSTAVO ZUBIETA M.D. * IPPA *” Date: 20 Mar 98 16:16:43 Subject: Re: CMS Symposium X-mailer: Pegasus Mail v2.3 (R5). To: “John Reeves”
Dear Jack: Thank you for your E-mail of march 15. We were out of town and just returned yesterday.
You wrote: > I have the abstract “Incidence of Disease at High Altitude in La Paz > Bolivia”. Will that be the subject of your presentation in the CMS session?
Yes, we consider this to be more adequate to our field than in the high altitude population in the world symposium. In fact we meant to deal more with CMS in this presentation.
> How long are you planning to talk? Would 20 minutes be fine? Keep in mind that we are hoping for as much time as possible for discussion. One of the main question that will require discussion is that of the definition of CMS, so that we can all play from the same sheet music. In your case, do you include or exclude persons with chronic lung disease in the CMS group?
Following is the summary of the modest opinion of my father and myself, from many years of observations in the bowl-shaped city of La Paz to El Alto (between 3100m and 4100m), with much CMS in a population above 1.2 million:
1) In our concept, CMS or Monge’s disease are adequate denominations for a disease present only in hypoxic conditions due mainly to respiratory and ventilatory alterations of different etiopathogenesis, some complicated by other alterations such as kidney disease, arterial hypertension, and so on.
2) CMS at high altitude is expressed as cyanosis and low arterial saturation which gives rise to pulmonary hypertension and increased polycythemia, as compensatory mechanisms of adaptation to the disease under hypoxic conditions.
3) CMS is irreversible in diseases like pulmonary fibrosis, and reversible in chronic bronchitis, for example. If the arterial blood is completely saturated at 98%, as such is the case when the subject descends to sea level, there is a regression of the symptoms and signs. Giving continuous oxygen administration to a patient with COPD at sea level, will achieve similar results.
4) Respiratory diseases are the same at high altitude, in etiopathogenesis as those of sea level; but the impaired respiratory function, with low oxygen saturation, below the plateau of the saturation curve (in the steep part), shows us what we know as CMS or Monge’s disease.
5) Since CMS is a common denominator of diverse diseases of the respiratory system, each case should be diagnosed and treated according to the etiopathogenesis. It seems also evident that some subjects are more prone to suffer pulmonary diseases. Similarly, men have a greater tendency to develop pulmonary disease, than women and consequently are more susceptible to develop CMS. So, hoping to answer your question: The confusion arrives because the classical description of Monge’s disease in 1928, expressed that there is no pulmonary anatomical or functional alterations, not able to become evident at the time, due to the lack of modern technology that we have nowadays. Not all patients with respiratory disease at high altitude develop CMS. Some pulmonary diseases alter as a sequelae the pulmonary function, like impaired diffusion, uneven ventilation, increased shunt, or hypoventilation. These lead to low saturations in hypoxic conditions and to CMS. Please read our article New Concepts on Chronic Mountain Sickness.
We enjoyed preparing these comments, and if you should have any doubts, questions or comments please feel free to send us an E- mail. We were hoping to meet you in Cuzco, and inquired about you but they said you were in Russia. We were supposed to go the meeting in Ukraine invited by Beloshitsky. We ran into many problems. We couldn’t get to Ukraine from Moscow. We will tell you more when we meet in Japan.
Gustavo Sr. & Gustavo Jr. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Gustavo Zubieta, M.D. HIGH ALTITUDE PATHOLOGY INSTITUTE * IPPA * Av. Saavedra 2302 Tel: 591-2-368734 P.O. BOX 2852 Fax: 591-2-229504 La Paz, Bolivia E-mail: email@example.com
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