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



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




Trauma Related High-Altitude Pulmonary Edema

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


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

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


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.