Tatum Simonson and Altitude Adaption: Physiologic and Genetic

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 orangered 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 EPAS1has 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.

 

 

 

A Query on Mt Quandary

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 3I 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.

Can I take my child up a 14er?

There are over fifty 14ers in Colorado. A 14er is a mountain with an elevation of at least 14,000 feet. If summited, these majestic peaks afford their climbers spectacular views of the surrounding landscape. Being that many people within Colorado – and those who come to visit – are active, a question often voiced by parents is: “Can my child hike up a 14er with me?” Unfortunately, there is no straightforward answer to this question and the simplest response is: it depends.

According to recent research, it appears that children are largely similar to adults when it comes to adapting to higher elevations. Research examined children’s short-term cardiorespiratory adaptation, incidence of acute mountain sickness, hypoxic ventilatory response, and maximal exercise capacity and found little variance between adults and children (Garlick, O’Connor, & Shubkin, 2017).

When CAN you take your child up a 14er? There are a multitude of factors that affect when and if a child can climb a 14er. For example, children develop and mature at different rates. This might affect whether your 11-year-old is able to climb a 14er, compared to someone else’s 11-year-old. Additionally, some children grow up being exposed to technical hikes and climbs, while others are not. This affects ability level and is certainly something to keep in mind (Provance, n.d.). Another factor to keep in mind is whether you’re child has an underlying condition. For example, conditions such as congenital heart disease, asthma, sickle cell anemia, an upper respiratory infection, or an ear infection can significantly increase the risk for high altitude illnesses (Garlick, O’Connor, & Shubkin, 2017, p. 6). Yet another factor is whether you live at altitude or are visiting from a lower elevation. There is a strong recommendation for those individuals traveling from a lower altitude to take some time to acclimate. Spending a night or two at an intermediate altitude is recommended. Additionally, be mindful not to overdo it when you do ascend to a higher elevation: stay hydrated and don’t overexert yourself. If you decide to climb a 14er, it is imperative that you give your body at least a few days to acclimate to the altitude (“How can I optimize my health at high altitude?”, 2016).

So, what’s the bottom line? Since it isn’t possible to place a concrete age on when it’s okay for your child to climb a 14er, it is ultimately up to you to know you’re child’s limits and to decide if such a challenging hike is right for you and them. The most important thing is to make sure that everyone remains safe.

If you do decide to set out on the challenge of hiking up a 14er, there are some things to remember in order to keep yourself and your child as safe as possible and ensure that the hike is an enjoyable experience for all (Kirkland, 2015):

  • Set out early: Summiting the peak by noon is recommended in order to avoid afternoon weather, thunderstorms, and potential lightning strikes.
  • Start slow and easy: It’s important for you to determine whether or not you’re child will be able to summit a 14er. Start with easy hikes and build up over time so that you have a good understanding of your child’s abilities.
  • Know the weather forecast: Check the weather before you set out to prevent getting stuck in a storm.
  • Clothing: Wear appropriate clothing. It is important to layer since it can be colder on top of the mountain. Additionally, it is important to wear clothing that protects you from the elements (including the sun!).
  • Protect yourself from the sun: The sun can be very strong when one is high up. It is very important to ensure that your child is adequately protected from the sun: sunscreen, clothing, etc.
  • Food and Fluids: Bring adequate nutrition and hydration.
  • Be prepared to turn around ahead of time: There are many things that could cause you to turn around. It’s very important to accept ahead of time that you might not manage to summit the peak and to accept that’s okay.
  • High altitude illness: It is incredibly important for you to know the symptoms of high altitude illness and be prepared to turn around should your child exhibit any of them. Symptoms of high altitude illness include: fussiness or irritability, refusal to eat, lack of energy, nausea and/or vomiting, dizziness, and light headedness (Provance, n.d.).

References:

Garlick, V., O’Connor, A., & Shubkin, C. D. (2017). High-altitude illness in the pediatric population: A review of the literature on prevention and treatment. Current Opinion in Pediatrics, doi:10.1097/MOP.0000000000000519

How can I optimize my health at high altitude? (2016). Retrieved from http://www.altitudemedicine.org/optimizing-health-at-altitude/

Kirkland, E. (2015, May). Taking kids to new heights: Hiking Colorado’s “14er” mountains. Retrieved from http://www.outdoorfamiliesonline.com/hiking-colorados-14er-mountains/

Provance, A.J. (n.d.). What age can my child start hiking fourteeners? Retrieved from https://www.childrenscolorado.org/conditions-and-advice/new-and-featured-articles/sports-safety/when-can-kids-start-hiking-fourteeners/

Rianne Smeele, BSN, RN, Regis University FNP Student

Does Hypoxia Prevent Cancer?

Summit Daily News recently published an article based on research in the Journal of the American Medical Association showing Summit County                                                                                                       with the lowest cancer rate in the nation FOR 30 YEARS. Are people moving away when they get cancer? No, they are treated in Vail, Denver                                                                                                      and now the St. Anthony Summit Medical Center.  Do we have fewer older people? No, there is a large percentage of retired residents.

The report shows stark differences in regional cancer death rates : detailed estimates for deaths from nearly 30 types of cancer in all 3,100 U.S. counties for over 35 years.From 1980 to 2014, the U.S. death rate per 100,000 people for all cancers combined dropped from about 240 to 192 — a 20 percent decline. More than 19 million Americans died from cancer during that time, the study found. Healthy lifestyle with low rates of obesity and smoking and increased physical activity contribute to low cancer rates in the mountains.

The picture was rosiest the Colorado ski country, where cancer deaths per 100,000 residents dropped by almost half, from 130 in 1980 to just 70 in 2014;

The air is thinner up here!

More and more people of all ages travel to  and reside in the mountains. Scientists and health care providers are just beginning to discover the effect of high altitude on health.

I have practiced medicine in Frisco, Colorado at 9,100 feet since 2000. Before that I worked on Saipan at sea level for 20 years. The difference has made me aware of special considerations when caring for people from newborns to retirees at high altitude. Simple measures can be taken to save a vacation or preserve an active life style in the mountains.  All visitors who are not pregnant should consider taking Diamox (acetazolamide) starting two days before travel. Tourists and residents should buy an inexpensive home pulse oximeter to monitor oxygen levels.  Anyone staying for more than a week should pursue testing for night time hypoxia and pulmonary hypertension when experiencing difficulty sleeping, fatigue or trouble breathing

Read articles on the Ebert Family Clinic Website for more information. I will add new information, discuss symptoms and diagnoses, and respond to questions. We have a power point available to interested groups. Personal evaluations and consults can be scheduled at Ebert Family Clinic with myself for children and Laura Amedro FNP for adults or children

Hi altitude Conference- peoples final.