Category Archives: High Altitude

High Altitude, Medicine

Altitude research partnership with University of Heidelberg and University of California in San Diego

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Two of the most prominent centers for altitude research in the world are University of Heidelberg, led by Peter Bartsch MD and                                                                                                               University of California in San Diego, with John West MD.

Dr Christine Ebert-Santos met with five of their affiliated researchers while in San Diego where she presented her case on                                                                                                                    trauma and HAPE at the American Thoracic Society conference.

They are interested in partnering with Ebert Family Clinic for a study related

to the genetics of high altitude, using our area as an intermediate altitude location.

Photo of Dr. Chris with UCSD staff  Tatum Simonson PhD, facing, Jeremy Orr MD, behind her,

Jeremy Sieker MD PhD candidate from Colorado, and University of Heidelberg staff  Heimo Mairbaurl PhD and Christina Eichstaedt PhD

Acclimation, Health, High Altitude

Mountains and Caffeine

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Effects of Caffeine at High Altitude

Visitors travelling to high altitude destinations have been known to avoid coffee/caffeine intake in order to avoid the dreaded symptoms of acute mountain sickness. The theory is that caffeine leads to dehydration, which then predisposes the individual to acute mountain sickness. A few symptoms of dehydration include headache, lethargy, confusion, weakness, nausea and vomiting. Similarly, symptoms of acute mountain sickness include fatigue, headache, nausea, vomiting, shortness of breath and difficulty sleeping. Although the symptoms of dehydration and acute mountain sickness are very similar, there is no evidence to support this claim that dehydration predisposes an individual to acute mountain sickness.1 Thus, the diuretic effect of coffee and caffeine are often exaggerated. Individuals that are accustomed to drinking 12 oz. of coffee rarely suffer from the diuretic effect of the beverage.1

The condition of acute mountain sickness is a response to hypoxia in the brain’s vascular circulation that causes an increase in the release of a neurotransmitter called adenosine. Adenosine binds to adenosine receptors found on the inner lining of cerebral blood vessels, causing vasodilation of the blood vessels in an attempt to increase the flow of oxygen and nutrient-rich blood to the brain. This increase in cerebral blood flow, however, is painful and causes many of the above-mentioned symptoms of acute mountain sickness.

Caffeine, in contrast, counteracts these effects of adenosine in the brain’s circulation by causing vasoconstriction of those cerebral blood vessels, decreasing blood flow within the brain. Therefore, it is likely that caffeine can help prevent the onset of acute mountain sickness because of its ability to decrease cerebral vasodilation in response to hypoxia at high altitude.1 Caffeine is included in several over-the-counter headache medications, such as Excedrin Migraine, exactly for this purpose.

While there is no clinical data exhibiting that caffeine increases the rate at which individuals acclimate to living at high altitude from sea level, physiologic studies suggest that caffeine is helpful in increasing ventilation and decreasing hypoxia. Caffeine stimulates chemoreceptors in the brain and carotid arteries, altering the brainstem’s respiratory center in the medulla oblongata to become more sensitive to low blood oxygen saturation. As a result of this increased sensitivity to hypoxia, the lungs and respiratory muscles unconsciously increase their activity to increase resting ventilation rate and increase blood oxygen saturation.

My Experience

During my six weeks at the Ebert Family Clinic for my pediatric medicine rotation, I measured my blood oxygen levels before and after drinking 12 oz of coffee. My results can be found in Table 2.

Table 2. Six-week average blood oxygen saturation pre- and post-consumption of 12 oz. coffee

Pre-coffee oxygen saturation average: Post-coffee oxygen saturation average:
Week 1 91% 94%
Week 2 90% 92%
Week 3 91% 93%
Week 4 92% 94%
Week 5 92% 93%
Week 6 91% 93%

While these results are an anecdotal summary of my own experience living at high altitude and drinking coffee for six-weeks, drinking 12 oz. of coffee showed an average increase of blood oxygenation of 2%.

Caffeine Study at Everest

One study conducted at the base camp of Mt. Everest (17,600 ft) studied the 24-hour effect of caffeine in black tea ingested by one study group compared to a placebo group that only drank water. Both groups ingested the same volumes of liquid in the 24 hours. The study found that both groups had identical urine amounts at the end of the study, suggesting that caffeine did not lead to dehydration. Additionally, the tea-drinking group reported less fatigue and better mood compared to the placebo group.1

Caffeine Withdrawal at High Altitude

Caffeine cessation in fear of dehydration while travelling to high altitude destinations often leads to an exacerbated withdrawal reaction from caffeine, mimicking the symptoms of acute mountain sickness. This is due to the up-regulation, of adenosine receptors in the brain that become uninhibited in the absence of caffeine. As a result, adenosine binds to the increased amount of adenosine receptors in the brain causing excessive cerebral vasodilation and subsequent headache, nausea, vomiting, weakness, lethargy and confusion. Therefore, regular coffee drinkers or any type of caffeine users should avoid abrupt cessation of caffeine intake while traveling from sea level to high altitude.1

Future Studies

The above mentioned studies have not studied the effects of caffeine in caffeine-tolerant vs. caffeine-naïve individuals, but a trial of caffeine in the form of either coffee, tea or pill would be worthwhile in otherwise healthy individuals suffering from symptoms of acute mountain sickness while visiting high altitude locations. Future studies would benefit from comparing the effects of caffeine on caffeine tolerant individuals and individuals who do not consume caffeine on a regular basis. However, individuals must always consult their health care provider to determine if it is safe to use caffeine prior to consumption of caffeine products.

Michael Peterson, PA-S

University of St. Francis, Physician Assistant Program

Health, High Altitude, Medicine

It’s so exciting to be CITED!

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Today I opened the March 2018 issue of the Journal of High Altitude Medicine and Biology.

What a surprise!

My publication  was cited in an article on pulmonary edema in children written by professors in the pulmonary department at Children’s Hospital of Colorado!  This is actually the first indication I’ve had that anyone beside me believes in the entity I called Mountain resident HAPE in the article published in the same journal last September.

Dr. Liptzin and her colleagues wrote, “We briefly describe high-altitude illnesses and propose recommendations for evaluation and treatment of HAPE in children as well as investigate the underlying contributors to HAPE. We discuss high-altitude resident pulmonary edema (HARPE), a new entity (Ebert-Santos, 2017). We will also highlight areas for further research.” The authors do not recommend prophylactic treatment for HAPE. Rather they recommend that when symptoms develop, supplemental oxygen be applied and  descent to lower altitude.

Acclimation, Health, High Altitude

Summit v.s. Saipan: Running

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Dr. Chris and Jacqueline, her niece from Guam, enjoy the Beach Road rec path in Saipan

When I lived on Saipan in the Pacific and visited my parents in Breckenridge I noted that my 10k  times were just as good at 9000 ft with humidity around 27% and temperatures in the 70’s as at sea level with 80% humidity and temperatures in the 80’s. Last month I had the same experience, in reverse: living at high altitude and visiting Saipan. Reading our blog on asthma, I attribute that to the lower viscosity of air and lower air pressure in the mountains compared to the high density of water vapor in the islands.  Both locations are beautiful and inspiring places to run!

Acclimation, Genetics, High Altitude

Tatum Simonson and Altitude Adaption: Physiologic and Genetic

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Tatum Simonson is a researcher at the University of California, San Diego who is interested in high altitude medicine: specifically, how high altitude adaptations can, over hundreds of generations, become part of our genes. I read one of her publications called Altitude Adaptation: A Glimpse Through Various Lenses. It delves into the research that has been done on physiologic and genomic changes of high altitude inhabitants and how these two factors coincide.

When looking at this information, it is important to remember that the reason high altitude is so much different from sea level or lower altitude is the oxygen in the air. It is not necessarily the percentage of the oxygen in the air, because the air is 20.9% oxygen at all altitudes. It is actually the lower air pressure that makes it feel like there is less oxygen. The air pressure comes from the weight of the air above us in the atmosphere. The further you go up, the less atmosphere there is above you to press down, and therefore less air pressure. Boyle’s law (whoa physics!) basically says that because of the lower pressure, in a given volume of air there are fewer molecules. Because there are fewer molecules of everything, the percentage of oxygen remains 20.9% but it feels like there is less oxygen in the air.

This is all to say that organisms have to adapt to this lower air pressure and less molecules in a given volume. Things that we know are affected include the saturation of oxygen of our blood. With less air pressure to drive the saturation of our blood with oxygen, sometimes it leads to low oxygen levels, or hypoxia. Hypoxia is detrimental because our body needs oxygen for our cells to function.

Simonson looks at 3 populations that have lived at high altitudes (3500m-4500m or 11,483ft-14,764ft) for hundreds of generations: Qinghai-Tibetan Plateau, Andean Altiplano, and Semien Plateau of Ethiopia (see map below). In her paper she goes further into the history of these populations and the uncertainty that exists with their timeline, but for our purposes just know that these populations have inhabited these high altitude areas for anywhere from 5,000-70,000 years.

Figure 1. Map with three locations where high-altitude adapted populations have lived for hundreds of generations. (Image modified from http://www.nasa.gov/topics/earth/features/20090629.html; low elevations are purple, medium elevations are greens and yellows, and high elevations are orange, red and white.) Tatum S. Simonson. High Alt Med Biol. 2015 Jun 1;16(2):125-137.

The first lens she looks through is physiologic, or how the body functions. There has been extensive research in this lens, summarized below.

  • Increased common iliac blood flow into uterine arteries in Tibetan and Andeans leads to increased utero-placental oxygen delivery at altitude, allowing less growth restriction. In other words, Tibetan and Andean populations have increased the blood flow to the growing fetus to help it grow more like someone living at lower altitudes. Furthermore, some studies show that their babies are actually bigger.
  • Tibetan and Amhara Ethiopian populations show the characteristic increase in hemoglobin levels that has long been associated with travelers to high altitude, but to a much lower extent than someone who has just traveled to altitude (i.e. native lowlander). This is in contrast even with Andean populations, who have higher hemoglobin levels than Tibetans. The Tibetan and Amhara Ethiopian populations don’t necessarily need a higher level of hemoglobin (molecule that carries oxygen) to get the oxygen that they need to their tissues.
  • Differences in the control of breathing: the hypoxic ventilation response is an increase in ventilation that is induced by low oxygen levels. The research shows that Tibetans exhibit an elevated hypoxic ventilation response while Andeans exhibit a blunted response.
  • Tibetan and Sherpa have been shown to have higher heart rates than lowlanders at altitude, as well as increased cardiac output, or blood that they are able to pump out of their hearts. There are also differences in the energy sources that some high altitude populations use for their heart to pump.
  • There are certain adaptive changes in skeletal muscle that Sherpa populations have made as well. Specifically, increased small blood vessels and increased maximal oxygen consumption.

The second lens is genomic, or the evidence for different genes in highlanders that have allowed them to survive and thrive at higher altitudes. One theory is that the ancestors of modern day highlanders had specific genes that gave them traits that were favorable for surviving at high altitudes. By matter of Darwinian selection, these genetic variants were passed down favorably over generations.

  • Many genes studies are involved in the hypoxia-inducible factor (HIF) pathway, which is involved in regulating various responses to hypoxia including making new blood vessels, making new red blood cells, iron regulation, and metabolism.
  • Specific genes studied include EPAS1 – has been associated with low (within sea level range rather than elevated) hemoglobin in Tibetans at altitude discussed above. EGLN1 and PPARA have also been associated with hemoglobin concentration changes.
  • There are many other specific genes that have been associated with specific adaptive changes for these high altitude populations.

It is important to realize the physiologic and genetic components of adaptation to high altitude environment. Simonson sums it up best herself:

“Understanding the associations between genetic and physiological variation in highlanders has additional application for understanding maladaptive and general responses to hypoxia, which remain an important biomedical component of hypoxia research. This is also of clinical value when considering distinct and shared hypoxia-associated genetic variants and combinations thereof may contribute to physiological responses in residents and visitors to the environmental hypoxia at altitude as well as chronic…or intermittent…states of hypoxia.”

I was happy to read this article and see how high altitude medicine may be affected by genomics in the not-so-distant future. Hopefully you learned something about hypoxia, physiologic and genetic adaptations!

Hannah Evans-Hamer, MD

 

Resources:

Simonson T. Altitude Adaptation: A Glimpse Through Various Lenses. High Alt Med Biol. 2015 Jun; 16(2):125-37. PMID: 26070057; PMCID: PMC4490743.

 

 

 

High Altitude, Medicine

Trauma Related High-Altitude Pulmonary Edema

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HAPE Poster

Dr. Chris will be presenting this poster at the American Thoracic Society International Conference in San Diego in May of this year! This is an exciting opportunity that will spread knowledge of high altitude medicine with the leading researchers in the field. In addition, she hopes to have this case study published to raise awareness among other healthcare providers practicing at any altitude about the potential health complications associated with rapid changes in elevation.

Katie Newton, PA-S
University of St. Francis
Albuquerque, NM

 

Acclimation, High Altitude

Reentry High Altitude Pulmonary Edema (HAPE) in High Altitude Residents!

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When High Altitude Pulmonary Edema (HAPE) is diagnosed, one often thinks of the diagnosis in relation to patients who have lived long term in low/sea level altitudes coming to high altitudes for the first time. However, a new study conducted by Santosh Baniya based out of the Himalayas suggest there is a subset of HAPE in which long term high altitude residents can fall ill to HAPE upon reentry to high altitudes after even a brief stay at lower altitudes.

Baniya’s study is based off a case report of an otherwise healthy pediatric patient who was diagnosed with HAPE after returning to his village of Manag (3500m) after a winter in Besisahar (760m)- a trip that was done multiple times in his life time with no complications. One change surrounding this diagnosis was a recent construction of a road between the two villages that decreased the usual travel time from a span of several days to a single day. The pathophysiologic explanation behind this phenomenon is thought to be caused by the descent of high altitude residents to lower altitudes, leading to a decrease in the red cell mass and a compensatory rise in plasma volume, which then in turn predisposes an individual to pulmonary edema once they return to high altitudes. Had the patient taken the original route of travel- it is likely that the gradual ascent would’ve allowed his body to acclimate to the altitude change and the red cell mass and plasma levels would’ve adjusted accordingly. However, due to the decrease in overall travel time the excess plasma levels led to pulmonary edema. Manifestation of this included shortness of breath, respiratory distress, and hypoxia (an oxygen saturation of 44% in this case). Treatment included high-flow oxygen, dexamethasone to help with air way swelling, and descent to lower altitudes which resulted in immediate marked improvement.

The remarkable aspect of this case- and the reason it was published- is that the doctors in a high altitude community failed to recognize a condition familiar to medical providers in the mountains here in Colorado. More importantly the clinical symptoms that we describe here are also pertinent to Mountain Resident HAPE and Trauma Related HAPE, which is often misdiagnosed by experts in Denver and other lower altitude communities outside of Colorado. Understanding the prevalence of this phenomenon is of utmost importance as an incorrect diagnosis of influenza, pneumonia or asthma could lead to fatal consequences- as oxygen does not treat these conditions. Proper recognition, diagnosis and treatment with oxygen, rest, and if severe enough, descent into lower altitudes need to be carried out promptly for effective treatment.

 

Garkie Zhu, PA-S3
MCPHS PA Program

Reference:

Baniya, S. (2017). Reentry High Altitude Pulmonary Edema in the Himalayas. High Altitude Medicine & Biology,18(4), 425-427. Retrieved January 23, 2018.

Ebert-Santos, C. (2017). High-Altitude Pulmonary Edema in Mountain Community Residents. HIGH ALTITUDE MEDICINE & BIOLOGY, 18(3), 278-284. Retrieved February 2, 2018.

Health, High Altitude, Medicine

A Query on Mt Quandary

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A personal story of acute mountain sickness (AMS)

Disturbing the “Locals”

“Race ya down”, my friend Liz took off from the summit of Mt. Quandary. Ahead of us stood a 2 mile scrabble through a boulder field with a 1 mile decent down a winding trail through the forest where we would descend from 14,265’ to 10,850’. In my experience, a 6 mile hike with 3,400 vertical feet was no feat. However, something was different as we approached the cars at the end of the hike. I noticed the start of a headache and I held onto the car to keep myself from swaying while taking off my boots. Thinking this was merely dehydration I finished my 3 liters of water – but that did not help. Once in the car my head continued to throb as we drove over Hoosier pass. Incoherently I mentioned that we should stop for Gatorade but the 64 oz of Gatorade did not abate my symptoms. In fact they worsened, my symptoms included severe dizziness, nausea, and a pounding headache. While my memory was hazy I knew this was not dehydration, maybe this was acute mountain sickness? But how could it be? I was in shape, lived at 5,400’, and this was my 5th 14er that summer. Was it possible to have AMS on the same peak I had climbed just weeks prior?

Standing on the summit of Mt. Quandary

My name is Chris Whitcomb and I am a 3rd year PA student at the University of Colorado. This story is all too familiar for anyone who spends time at elevation. Thankfully by the time we hit Idaho Springs, 7,526’, my symptoms dramatically improved. After reviewing my case and talking it over with my peers I believe that I developed AMS with some elements of HACE mixed in. A quick calculation of the Lake Louise Score came in at 6, which would classify this episode as “severe AMS”.

Who is most susceptible to AMS?

A prospective study analyzed a total of 11,182 workers on the Quighai-Tibet railroad in Tibet. This study identified 6 independent risk factors for AMS such as: rapid ascent to elevations above 3500 m (11482’), sea-level or lowland newcomers, young people of age, heavy physical exertion, obesity, or SaO2 below 801.  Another study in 2013 looked into various other predictive indexes for AMS and found that the level of activity (higher activity) and sex (male>female) lead to increased odds of AMS 2. A quick review of the above criteria showed that I was the perfect demographic for AMS. I am a young male who was exerting myself physically at altitude.

Will this stop me from hiking at elevation?

Not one chance! Last summer alone my wife and I backpacked and hiked over 250 miles in Colorado. Since the incident I now make sure that I have the ability to seek lower elevation if needed during all our outdoor adventures. I also pay close attention to how I am feeling as we ascend.

Should I take acetazolamine/Diamox before backpacking trips because of my past AMS episode?

A meta-analysis in 2015 looked at 7021 individuals to see if a past episode of AMS warranted medication to prevent future AMS episodes. Interestingly enough they found that the literature did not support it. This was in part due to the sporadic nature of AMS 3. I personally do not take a prophylactic medication before hiking at elevation, but this would be a great conversation to have with your medical provider if you are at all concerned.

Chris Whitcomb, PA-S3
University of Colorado
Class of 2018

References

  1. Wu TY, Ding SQ, Liu JL, Jia JH, Chai ZC, Dai RC. Who are more at risk for acute mountain sickness: a prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula. Chin Med J. 2012;125(8):1393-400.
  2. Beidleman BA, Tighiouart H, Schmid CH, Fulco CS, Muza SR. Predictive models of acute mountain sickness after rapid ascent to various altitudes. Med Sci Sports Exerc. 2013;45(4):792-800.
  3. Macinnis MJ, Lohse KR, Strong JK, Koehle MS. Is previous history a reliable predictor for acute mountain sickness susceptibility? A meta-analysis of diagnostic accuracy. Br J Sports Med. 2015;49(2):69-75.
Health, High Altitude, Medicine

High Altitude Increases Longevity!

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A new study completed by Gustavo R. Zubieta-Calleja based out of La Paz Bolivia has shown that residents of high altitude live longer and healthier lives then their sea-level companions. According to the study there are several things that high altitude offers that contribute to increased longevity of residents. Residents at high altitudes have adapted to life with less oxygen (hypoxia) thus enabling their bodies to be more suited for a longer life. The study also points out that at higher altitudes there is less of an occurrence of asthma and other lung diseases, this can be attributed to the dryness of the air and the abundance of sunshine typically found at higher altitudes.

Dr. Zubieta-Calleja goes on to point out that living at high altitude can improve longevity in many other ways as well.

  •  It alters the genetic make up populations, making them stronger and more suited to difficult living conditions
  • High altitude residents are less susceptible to many diseases that sea-level residents need to be concerned with as well. This is due to the lack of mosquitos and many other disease-carrying             insects that are unable to survive at high altitude.
  • Increased exposure to sunshine increases the bodies Vitamin D levels providing us with benefits to our hearts and well as reducing our risk of some cancers.
  • High altitude also helps our hearts become stronger, thus working more effectively, while also increasing blood flow to our body and brains.
  •  The decrease in oxygen level at high altitude helps our lungs work more effectively and increases our ventilation.

Dr. Zubieta-Calleja’s research has shown that there are more residents over 90 and 100 years of age at high altitude then there are at comparable populations at sea-level. The study compared the city of Santa Cruz Bolivia with an elevation of 416m to La Paz Bolivia with an elevation of 3800m, both cities have a population around 2.7 million people. In Santa Cruz there were 158 residents older than 90 years of age verses 974 residents older than 90 in La Paz. The trend continues for those over 100 years of age as well. In Santa Cruz there are 6 residents over 100 years of age verses 48 residents older than 100 in La Paz. Dr. Zubieta-Calleja’s study shows that as altitude increases so does longevity.

 

 

Dr. Chris’ parents! Both in their 90’s and are happy residents of high altitude living.

 

Written by Rhea Teasley-Bennett FNP student

 

Reference

 

Zubieta-Calleja, G.R., & Zubieta-DeUrioste, N.A. (2017). Extended longevity at high altitude: Benefits of exposure to chronic hypoxia. BLDE University Journal of Health Sciences. 

Acclimation, Health, High Altitude, Medicine

Chronic Mountain Sickness

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Avinell Abdool

 

Chronic Mountain Sickness (CMS) is a pathological finding that is commonly found amongst individuals that have taken up permanent residence in high altitude environments (altitudes of over 8,200 feet)1. Clinical manifestations of CMS include but are not limited to the following1;

  • HA
  • Dizziness
  • Tinnitus
  • Breathlessness
  • Palpitations
  • Sleep Disturbances
  • Fatigue
  • Loss of appetite
  • Confusion
  • Cyanosis
  • Dilation of veins

 

CMS is the outcome of progressive loss of ventilation rate, which subsequently results in hypoxemia and polycythemia2. Polycythemia is defined as by excessive erythrocytosis (EE; Hb >/= 19g/dL for women and Hb >/= 21 g/dL for men) which along with a hypoxic environment can result in pulmonary hypertension2. In advanced conditions of Chronic Mountain Sickness there can be cor-pulmonlae and congestive heart failure2 .

A study was conducted in the University of San Diego by Dr. Gabriel Haddad that researched the adaption of the Peruvian population in high altitude conditions3. It was found that CMS is highest in the Andeans (approximately 18 %), lesser in Tibetans (1%-11%) and completely absent in the Ethiopian population3. From these data points it appeared that there was was a genetic correlation between CMS sufferers and ethnicity3. In addition, this finding added another factor that mystified the conclusive pathogenesis of CMS3. By understanding exact pathogenesis of CMS, it would not only benefit those who are at potential risk for the disease but also those living at sea level, where hypoxia plays a role in certain pathology ( such as stroke, cardiac ischemia, Obstructive sleep apnea and Sickle Cell Disease)3 .

A cohort of 94 individuals were gathered and were equally categorized into CMS and non CMS subjects3. These individuals originated from Cerro de Pasco, which has an elevation of greater than 14,000 feet3. Genetic tools and a custom algorithm were utilized and the researchers identified 11 regions on the genome that contained 38 genes that proved to be statistically significant3. Nine of the eleven genes were tested in fruit flies in hypoxic experiments3. The experiment consisted of fruit flies that had these genes and ones that did not have the genes3. It was concluded that individuals with these molecular adaptions were better able to adapt to physiological stress such as hypoxia when compared to individuals that did not have this adaption3. The results of this study allowed researchers to better understand the correlation between genetics and individuals who strive in hypoxic environments3.

 

 

Figure 1- D.melanogaster (fruit fly)3

 

 

Figure 2-Cerro de Pasco3

 

Bibliography

 

  1. Villafuerte FC, Corante N. Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment. High Altitude Medicine & Biology. 2016;17(2):61-69. doi:10.1089/ham.2016.0031.
  2. Chronic mountain sickness and high altitude pulmonary hypertension. High Altitude Medicine and Physiology 5E. 2012:333-346. doi:10.1201/b13633-23.
  3. Stobdan T, Akbari A, Azad P, et al. New Insights into the Genetic Basis of Monges Disease and Adaptation to High-Altitude. Molecular Biology and Evolution. 2017. doi:10.1093/molbev/msx239.