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Re-Entry HAPE: Leading Cause of Critical Illness in Mountain Teens

Health care providers and people who live at altitude often believe that living in the mountains protects from altitude related illness. And yes, there are many ways the body acclimatizes over days, weeks, months, and years, as addressed in previous blog entries. However, as a physician who has practiced in high altitude communities for over 20 years, my personal observation that we are still at risk for serious complications was reenforced by a recent publication by Dr. Santiago Ucrós at the Universidad de los Andes School of Medicine in Santa Fe de Bogotá, Colombia. His article, High altitude pulmonary edema in children: a systemic review, was published in the journal Pediatric Pulmonology in August 2022. He included 35 studies reporting 210 cases, ages 0-18 years, from 12 countries.

A chart titled "HAPE in Children" illustrates cases of high altitude pulmonary edema by country.

Consistent with our experience in Colorado, the most common ages were 6-10 years and second most common 11-15 years. I have not seen or read any reports of adults affected. Cases included two deaths, which I have also seen here.

I receive reports on any of my patients seen in urgent or emergency care. Accidents, avalanches, and suicide attempts are what we think of first needing emergency care in the mountains. However, the most common critical condition is Reentry HAPE. This is a form of pulmonary edema that can occur in children who are returning from a trip to lower altitude. Think visiting Grandma during school break.  Dr. Ucrós’ review also confirms that all presentations of HAPE (classic, as in visitors, reentry, and HARPE, resident children with no history of recent travel) are more common in males by a 2.6 to 1 ratio. Analysis of time spent at lower altitude before the episode showed a range of 1.6 to 30 days with a mean of 11.3 days. Mean time between arrival and onset of symptoms for all types of HAPE was 16.7 hours. The minimum altitude change reported in a HAPE case was 520 meters (1700 feet), which is the difference between Frisco, CO (Summit County) and Kremmling, CO (Grand County, the next county over). A new form of HAPE in high altitude residents who travel to higher altitude was designated HL-HAPE in this review.  A case report will be featured in an upcoming blog interview with a Summit County resident who traveled to Mt. Kilimanjaro.

As with all cases of HAPE, the victims develop a cough, sound congested as the fluid builds up in their lungs, have fatigue, exercise intolerance, with rapid onset over hours of exposure to altitude, usually above 8000 ft or 2500m. Oxygen saturations in this paper ranged from 55 to 79%. My patients have been as low at 39% in the emergency room.  Children presenting earlier or with milder cases come to the office with oxygen saturations in the 80’s. An underlying infection such as a cold or influenza is nearly always present and considered a contributing factor. Everyone living or visiting altitude should have an inexpensive pulse oximeter which can measure oxygen on a finger. Access to oxygen and immediate treatment for values under 89 can be life-saving.

The recurrence rate for all types of HAPE is about 20%. Most children never have another episode, but some have multiple. Preventive measures include slower return to altitude, such as a night in Denver, acetazolamide prescription taken two days before and two days after, and using oxygen for 24-48 hours on arrival. Most families learn to anticipate, prevent, or treat early and don’t need to see a health care provider after the first episode.

On January 26, 2023 I met with Dr. Ucrós and other high altitude scientists including Dr. Christina Eichstaedt, genetics expert at the University of Heidelberg in Germany, Dr. Deborah Liptzen, pediatric pulmonologist, and Dr. Dunbar Ivy, pediatric cardiologist, both from the University of Colorado and Children’s Hospital of Colorado, and Jose Antonio Castro-Rodríguez MD, PhD from the Pontifica Universidad Católica in Santiago de Chile.

We discussed possible genetic susceptibility to HAPE and hypoxia in newborns at altitude with plans to conduct studies in Bogotá and Summit County, Colorado.

Going Home to the Mountains Can Be Dangerous: Re-Entry HAPE (High Altitude Pulmonary Edema)

Louie was excited to get out on the slopes after spending Thanksgiving with family in Vermont. He got tired early and felt his breathing was harder than usual, leaving early to go home and rest. As a competitive skier he thought that was strange. But he was getting over a cold. He could not have imagined that in 24 hours he would be in the emergency room, fighting for his life.

Louie experienced a dangerous condition, set off by altitude, and inflammation from his “cold”, that caused his lungs to fill with fluid.  His oxygen saturation was 54 % instead of the normal 92, he had been vomiting and feeling very weak and short of breath. His blood tests showed dehydration, hypoxemia and acute kidney injury. His chest x-ray looked like a snowstorm. He was transferred to Children’s Hospital in Denver and admitted to the intensive care unit.

The diagnosis of Re-entry HAPE was confirmed by echocardiogram showing increased pressures in his lungs. He improved rapidly with oxygen and low altitude.

Re-entry HAPE is not rare, affecting several Summit County children every year.  Many do not come to medical attention because after their first episode parents carefully monitor their oxygen and have a concentrator available in their home when they return from travel. 

Medical providers may not be aware of this risk, expecting that children living at altitude are acclimatized. (See blog entry on Acclimatization vs. Adaptation, April 17, 2019) Re-entry HAPE seems to occur mostly in children between the ages of 4 and 15. Inflammation, such as a viral respiratory infection, seems to play a role.  Trauma may also predispose a returning resident to Re-entry HAPE, as described in our blog post from February 5, 2018, Trauma related High Altitude Pulmonary Edema

Louie agreed to share his story on our blog to help educate medical personnel and families living in the mountains about this dangerous condition. Further research will help define who is at risk. 

HARPE is the New HAPE

It took ten years for me to convince high altitude experts that children living in the mountains get high altitude pulmonary edema (HAPE) without leaving home. My observations were published in 2017 in the Journal of High Altitude Medicine and Biology,

High-Altitude Pulmonary Edema
in Mountain Community Residents

This week Dr. Jose A Castro-Rodriguez MD PhD ATSF discussed HAPE in children at the 8th World Hypoxia conference in La Paz including the now renamed high altitude resident pulmonary edema (HARPE) in his presentation.

Dr. Castro-Rodriguez emphasized the importance of recognizing the three forms of HAPE, including reentry HAPE when children return to the mountains from vacation, since these can be life threatening.

My work has been cited in articles by pulmonologists Deborah Liptzin and Dunbar Ivy from Children’s Hospital of Colorado and geneticist Christine Eichstaedt and her team at the University of Heidelberg.

At Ebert Family Clinic we give every patient/family a free pulse oximeter. The ability to measure the oxygen saturation of anyone with cough, congestion, or fatigue can facilitate early treatment with oxygen and prevent visits to the emergency room, hospital and intensive care unit.

I recently received first prize for a poster presentation on HARPE at the fall Colorado Medical Society meeting, and second prize for a poster on Trauma and HAPE.

For more information about HAPE, HARPE and Trauma-related HAPE, see previous blog entries.

References

Ebert-Santos C. High-Altitude Pulmonary Edema in Mountain Community Residents. High Alt Med Biol. 2017 Sep;18(3):278-284. doi: 10.1089/ham.2016.0100. Epub 2017 Aug 28. PMID: 28846035.

Giesenhagen AM, Ivy DD, Brinton JT, Meier MR, Weinman JP, Liptzin DR. High Altitude Pulmonary Edema in Children: A Single Referral Center Evaluation. J Pediatr. 2019 Jul;210:106-111. doi: 10.1016/j.jpeds.2019.02.028. Epub 2019 Apr 17. PMID: 31005280; PMCID: PMC6592742.

Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018 Mar;19(1):91-98. doi: 10.1089/ham.2017.0096. Epub 2018 Feb 22. PMID: 29470103; PMCID: PMC5905943.

Eichstaedt CA, Mairbäurl H, Song J, Benjamin N, Fischer C, Dehnert C, Schommer K, Berger MM, Bärtsch P, Grünig E, Hinderhofer K. Genetic Predisposition to High-Altitude Pulmonary Edema. High Alt Med Biol. 2020 Mar;21(1):28-36. doi: 10.1089/ham.2019.0083. Epub 2020 Jan 23. PMID: 31976756.

High-Altitude Pulmonary Edema is not just for tourists

HAPE can affect long term locals too. There is no specific test to diagnosis HAPE leading to delayed treatment or improper treatment, including death.

HAPE is defined as fluid accumulation in the lungs when an individual spends about 48 hours at elevations of 8,200 feet or higher. This can occur when 1) tourists who are not accumulated to high altitudes appropriately 2) locals who re-enter high altitude after being at lower elevation for a period of time or 3) long term residents who develop an illness.

What are the signs and symptoms you ask? Exhaustion, dyspnea on exertion, productive cough, tachypnea, tachycardia, low oxygen saturation levels, and crackles upon lung assessments are the most common to be seen. These are very generic symptoms and resemble many other diseases, such as pneumonia and asthma, leading to misdiagnosis and improper treatment.

How is HAPE treated?

The answer is simple, oxygen. The body is being deprived of oxygen and is unable to feed our cells. By giving oxygen (either through an artificial source or returning to lower elevation) and allowing the body to rest, the body is able to meet its demand for oxygen and symptoms resolve. If one receives oxygen and symptoms do not improve, there is most likely an underlying cause that is contributing to the symptoms unrelated to HAPE.

A pulse oximeter is the easiest way that one can monitor their oxygen levels at home. This device can be purchased over the counter, relatively inexpensive, and easy to use. By placing the pulse oximeter on one’s finger, the device will read the individual’s oxygen level which should be greater than 90% (when at altitude). The heart rate will also be recorded which tends to be between 60-100 beats per minute when at rest for adults.

References

A new mechanism to prevent pulmonary edema in severe infections. Lung Disease News. (n.d.). Retrieved September 2, 2022, from https://lungdiseasenews.com/2015/01/14/researchers-discover-a-new-mechanism-to-prevent-pulmonary-edema-in-severe-infections/

Bhattarai, A., Acharya, S., Yadav, J. K., & Wilkes, M. (2019). Delayed-onset high altitude pulmonary edema: A case report. Wilderness & Environmental Medicine, 30(1), 90–92. https://doi.org/10.1016/j.wem.2018.11.002

Fixler, K. (2017, October 12). Colorado doctor: Health effects of living in mountains unknown to medical establishment. SummitDaily.com. Retrieved September 2, 2022, from https://www.summitdaily.com/news/summit-county-doctor-makes-a-case-for-high-altitude-disorder-that-affects-even-the-acclimated/

Interview with Retired Fighter Pilot Andrew Breithaupt: Altitude Earth and Sky

I had the honor of interviewing Andrew Breithaupt who recently retired from US Customs and Border Protection in the Department of Homeland Security where he served as an Air Interdiction Agent piloting multiple types of aircraft.  He currently serves as a Lieutenant Colonel on active duty for the US Army, stationed in Minneapolis, MN.  He began Army flight school in 1992 to become a helicopter pilot, ultimately qualifying in 4 different types of Army helicopters including the UH-1H, OH-58, AH-1, and the AH-64 Apache for which he became an Instructor Pilot training new Army aviators at Fort Rucker, Alabama.  Later he began his transition to fixed-wing aircraft in the civilian community. After nearly 10 years of Army active duty and multiple overseas tours, he was selected to enter service for US Customs and Border Protection where he served as a federal law enforcement agent for over 20 years, retired in December of 2021.  He holds his commercial pilot license for single engine & multi-engine fixed wing as well as rotorcraft with instrument privileges and aircraft type ratings. He has over 30 years of aviation experience and more than 2,500 hours of flight time over his career. I sat down to chat with him about his accomplished career and learn more about his aviation and altitude expertise.

In army flight school, specifically aeromedical training, he was taught the effects of aviation on the body. One of the first lessons they learned in their training was how to recognize the early warning signs of hypoxia. These include shortness of breath, dysphoria, nausea, vomiting and lightheadedness. This type of training is often done in altitude chambers, so trainees can experience these effects before they are in the air, including how aviation can affect your vestibular senses. A position change as simple as looking down to change a radio or instrument can completely disorient a pilot due to the change in direction of the fluid within the inner ear against the cilia. This can lead to the sensation that the plane has rotated and flying sideways. They are taught to trust their instruments because an overcorrection can lead to what they teach in flight school as a “death spiral.” The training is often done in a Barany Chair and simulates vestibular senses experienced during flight.

Elevation in Summit County, Colorado ranges from 7,947 feet to 14,270 feet, the highest peak being Gray’s Peak. With people living as high as 11,200 feet, as Andrew does at his home in Blue River located south of of Breckenridge, CO.  Andrew shared some very interesting aviation altitude requirements which might surprise some. He spent much of his career operating non-pressurized helicopters and Federal Aviation Regulations prohibited him from going between 10,000 feet to 12,000 feet for more than 30 minutes without oxygen. When flying above 12,000 feet, pilots are required to have supplemental oxygen regardless of the amount of time spent at that elevation depending on the category of aviation being conducted such as commercial operations. This is according to the CFR (Code of Federal Regulations) Part 135 which governs commercial aircraft operations. How interesting is it that pilots have these regulations, yet many people who live in Summit County or those summiting 14ers (peaks at 14,000 ft. or above) are at or above these elevations with no supplemental oxygen on a daily basis. When flying private aircraft, CFR part 91.211 specifies flight crew can fly without pressurization or supplemental O2 below 14,000 feet and passengers below 15,000 feet.

While in the Army, Andrew would rarely operate aircraft above 8,000 feet and would typically not have supplemental oxygen on board. They were trained to begin descent immediately if they were to notice the early signs of hypoxia. Keeping a pilot’s license requires strict annual or even semi-annual FAA physicals and continued training to ensure their bodies can withstand the effects of aviation.  As you can imagine those holding these licenses are some of the most fit men and women in the country.  Andrew rarely felt the effects of altitude even with altitude changes as great as 8,000 feet coming from sea level. He would typically remain at these elevations for two hours or less piloting non-pressurized aircraft.

To give some perspective, when you hop on a commercial flight for your next adventure these planes typically fly around 28,000 to 36,000 feet of elevation. When beginning the ascent, the aircraft pressure stabilizes at 6,000 to 8,000 feet, approximately when the dreaded “popping of the ears” is felt. Supplemental oxygen and quick donning masks are required on all these aircraft in case depressurization were to occur due to the rapid hypoxia which would occur at such high altitudes.

Andrew moved to Summit County in November of 2021 from Stafford, VA with his wife and five sons ages 24, 22, 19, 14, and 11.  Andrew and his family spent a significant amount of time in Summit County for snowboarding and skiing competitions and quickly fell in love with the area prior to spending the last 5 years living in Stuttgart, Germany. This is when they decided one day, they would become full-time residents of the county. They moved here for the “people, climate and lifestyle,” a combination I am learning is hard to beat outside of Summit County. With ski and snowboard season right around the corner, he and his family are excited to get back out on the slopes.   Andrew currently travels between his home in Blue River and Minneapolis for his position in the Army. With each trip back he feels his body more quickly adjust to the altitude changes. Thank you for your service Andrew, and welcome to the community!

Ellie Martini grew up in Richmond, VA and is currently a second-year Physician Assistant student at Drexel University in Philadelphia, PA. She completed her undergraduate degree at The College of William and Mary in Williamsburg, VA where she received her BS in Biology. Before PA school she worked as a rehab tech and medical scribe at an addiction clinic. In her free time she enjoys hiking, biking, group fitness, traveling and spending time with friends and family. 

Lost, Stranded, and Hungry in the Mountains of Western Colorado? A Mini Guide to Edible Plants

From backpacking and camping to skiing and snowboarding, there are plenty of activities outdoors in the Colorado high country. If you find yourself wandering around and lost without food in the mountains, there are several wild plants that you can eat. 

However, before you consume the delectable greens, there are a few precautions to take.

Moose shopping
  • Do not eat any wild plants unless you can positively identify them. There are iOS and Android apps that you can download prior to your hike to help distinguish plants, such as PictureThis and NatureID. 
  • Be aware of environmental factors such as pollution or animal waste. Avoid popular wild animal gathering areas.
  • Make sure you’re not allergic to the plant by rubbing it against your skin and observing for a reaction. If so, do not eat the plant. Before ingesting a large quantity, eat a small amount and check for a reaction. 

It may be difficult to cook if you did not come prepared with a portable stove, pots, and water, which could limit ways to enjoy vegetation. Here is a list of edible plants, how to identify them, where can they be found, and which part you can eat.

Wild plants

Dandelions (Taraxacum officinale): yellow ray florets that spread outward from center with toothy, deep-notched, hairless basal leaves and hollow stems. They can be found everywhere and anywhere. Every part of the dandelion plant is edible including the leaves and roots.

Yellow-green hemispheres bud in a bunch from green stems with pine needle-like leaves.

Pineapple Weed/ Wild Chamomile (Matricaria discoidea): the flower heads are cone-shaped and yellowish-green and do not have petals. Often found near walking paths and roadsides, harvest away from disturbed, polluted areas. If you’re feeling anxious about being lost, pineapple weed promotes  relaxation and sleep and serves as a  digestive aid.

Fireweed (Epilobium angustifolium): vibrant fuchsia flowers. Grows in disturbed areas and near recent burn zones. Eat the leaves when they are young as  adult leaves can stupefy you. Young shoot tips and roots are also edible. 

Wild onions (Allium cernuum): look for pink, lavender to white flowers with a strong scent of onion. They grow in the subalpine terrain and are found on moist hillsides and meadows. Caution: do not confuse with death camas. If it doesn’t smell like an onion and has pink flowers, it is not likely an onion.

Cattails (Typha latifolia or Typha angustifolia): typically 5-10 feet tall. Mature flower stalks resemble the tail of a cat. Grow by creek, river, ponds, and lakes. This whole plant is edible, from the top to the roots. Select from pollution-free areas as it is known to absorb toxins in the surrounding water.

Wild berries:

Wild strawberries (Fragaria virginiana): they are tiny compared to  store-bought. Can be identified by their blue-green leaves; small cluster of white flowers with a yellow center; and slightly hairy, long and slender red stems.

Huckleberries (Vaccinium spp): They grow in the high mountain acidic soil and flourish in the forest grounds underneath small, oval-shaped, pointed leaves. They resemble blueberries and have a distinguishable “crown” structure at the bottom of the berry. They can be red, maroon, dark blue, powder-blue, or purple-blue to almost black, and they range from translucent to opaque.

Deep blue berries stand out against bright red and green, waxy leaves.

Oregon grapes (Mahonia aquifolium): powder-blue berries, resembling juniper berries or blueberries, with spiny leaves similar to hollies that may have reddish tints.

Fun fact: The roots and bark of the plant contain a compound called berberine. Berberine has antimicrobial, antiviral, antifungal, and antibiotic properties.

Mushrooms

Brown whole and halved mushrooms lie on a green table with ridged, sponge-looking caps.

True morels (Morchella spp.): cone-shaped top with lots of deep crevices resembling a sponge. They will be hollow inside. A false morel will have a similar appearance on the outside but will not be hollow on the inside and are toxic. Morels are commonly found at the edge of forested areas where ash, aspen, elm, and oak trees live. Dead trees (forest wildfires) and old apple orchards are prime spots for morels.

Short, stubby mushrooms with white stems and brown camps stand in a row growing over grass.

Porcini (Boletus edulis): brown-capped mushrooms with thick, white stalks. Found at  high elevations of 10,500 and 11,200 ft in  areas with monsoon rains and sustained summer heat.

There are many more edible plants, flowers, berries, and mushrooms in the mountains. These are just 10 that can be easily identifiable and common in the Western Colorado landscapes. I recommend trying out the apps listed above and reading “Wild Edible Plants of Colorado” by Charles W. Kane, which includes 58 plants from various regions, each with details of use and preparation. Hopefully this post made you feel more prepared for your next adventure. 

Resources:

Davis, E., 2022. Fall plant tour: Frisco, CO | Wild Food Girl. [online] Wildfoodgirl.com. Available at: <https://wildfoodgirl.com/2012/eleven-edible-wild-plants-from-frisco-trailhead/> [Accessed 10 July 2022].

McGuire, P., 2022. 8 Delicious Foods to Forage in Colorado | Wild Berries…. [online] Uncovercolorado.com. Available at: <https://www.uncovercolorado.com/foraging-for-food-in-colorado/> [Accessed 10 July2022].

Rmhp.org. 2022. Edible Plants On The Western Slope | RMHP Blog. [online] Available at: <https://www.rmhp.org/blog/2020/march/foraging-for-edible-plants> [Accessed 10 July 2022].

Lifescapecolorado.com. 2022. [online] Available at: <https://lifescapecolorado.com/2014/01/edible-plants-of-colorado/> [Accessed 10 July 2022].

Pfaf.org. 2022. Plant Search Result. [online] Available at: <https://pfaf.org/user/DatabaseSearhResult.aspx> [Accessed 10 July 2022].

Cindy Hinh is a second-year Physician Assistant student at Red Rocks Community College in Arvada, CO. She grew up in southern Louisiana and received her undergraduate degree in Biology from Louisiana State University. Prior to PA school, she was a medical scribe in the emergency department and an urgent care tech. In her free time, she enjoys baking, cooking, going on food adventures, hiking, and spending time with family and friends.

Beneficial Effects of Chronic Hypoxia

Living in Summit County, Colorado has its perks – residents are within a 20 to 40 minute drive to five world class ski resorts, and some of the most beautiful Rocky Mountain trail systems are accessible right out our back door. With the endless opportunities drawing residents outdoors to partake in physical activity, it comes as no surprise that Summit County is considered one of the healthiest communities in the country. However, there may be more than meets the eye when it comes to explaining this, as it also has something to do with the thin air.

As a Summit County native, you have likely heard the term “hypoxia” or “hypoxemia” mentioned a time or two. So what does this mean? Simply put, these words describe the physiological condition that occurs when there is a deficiency in the amount of oxygen in the blood, resulting in decreased oxygen supply to the body’s tissues. When this occurs in the acute setting, it may result in symptoms such as headache, fatigue, nausea, and vomiting. These are common symptoms experienced by those with altitude illness, also known as acute mountain sickness. While these symptoms can cause extreme discomfort and may put a huge damper on a mountain vacation, they are not usually life threatening. However, in a small number of people, development of more serious conditions such as a high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) can occur. The treatment for all conditions related to altitude illness is oxygen, whether via return to lower elevations or by a portable oxygen concentrator that allows you to stay where you are. While altitude illness generally affects those who rapidly travel from sea level to our elevation, it has also been known to affect residents returning home to altitude, usually after a period of two or more weeks away. In a very small subset it can occur after a period of only a day or two. This generally occurs in those with a preexisting illness, where altitude exacerbates the condition.

While the acute effects of altitude can clearly have detrimental effects on one’s physical well-being, there is emerging research demonstrating that chronic hypoxia may actually come with several health benefits. Long time Summit County business owner and community pediatrician, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, has spent quite some time studying the effects of chronic high-altitude exposure, and recently attended and presented at the Chronic Hypoxia Symposium in La Paz, Bolivia, the highest capital city in the world.

It is important to first understand the adaptations that occur in our bodies as a result of long-term hypoxia. The ability to maintain oxygen balance is essential to our survival.

So how do those of us living in a place where each breath we take contains about ⅓ fewer oxygen molecules survive?

Simply put, we beef up our ability to transport oxygen throughout our body. To do this, our bodies, specifically the kidneys, lungs and brain increase their production of a hormone called erythropoietin, commonly known as EPO. This hormone signals the body to increase its production of red blood cells in the bone marrow. Red blood cells contain oxygen binding hemoglobin proteins that deliver oxygen to the body’s tissues. Thus, more red blood cells equal more oxygen-carrying capacity. In addition to increasing the ability to carry oxygen, our bodies also adapt on a cellular level by increasing the efficiency of energy-producing biochemical pathways, and by decreasing the use of oxygen consuming processes2. Furthermore, the response to chronic hypoxia stimulates the production of growth factors in the body that work to improve vascularization2, thus, increased ability for oxygenated blood to reach its destination. 

So, how can these things offer health benefit?

To start, it appears that adaptation to continuous hypoxia has cardio-protective effects, conferring defense against lethal myocardial injury caused by acute ischemia (lack of blood flow) and the subsequent injury caused by return of blood to the affected area3. The exact mechanism of how this occurs is not well understood, but it seems that heart tissue adapts to be better able to tolerate episodes of ischemia, making it more resistant to damage that could otherwise be done by decreased blood flow that occurs during what is commonly known as a heart attack. This same principle applied to ischemic brain damage when tested in rat subjects. Compared to their normoxic counterparts, rats pre-conditioned with hypoxia sustained less ischemic brain changes when subjected to carotid artery occlusion, suggesting neuroprotective effects of chronic hypoxia exposure4.

Additionally, it appears that altitude-adapted individuals may be better equipped to combat a pathological process known as endothelial dysfunction5. This process is a driving force in the development of atherosclerotic, coronary, and cerebrovascular artery disease. Altitude induces relative vasodilation of the body’s blood vessels compared to lowlanders2. A relaxing molecule known as nitric oxide, or NO, assists with causing this dilation, and in turn the resultant dilated blood vessels produce more of this compound5. The molecule has protective effects on the inner linings of blood vessels and helps to decrease the production of pro-inflammatory cytokines that damage the endothelium5. This damage is what kickstarts the cascade that leads to atherosclerosis in our arteries. Thus, a constant state of hypoxia-induced vasodilation may in fact decrease one’s risk of developing occlusive vascular disease. 

The topics mentioned above highlight a few of the proposed mechanisms by which chronic hypoxia may be beneficial to our health. However, do keep in mind that there are potential detrimental effects, including an increased incidence of pulmonary hypertension as well as exacerbation of preexisting conditions such as COPD, structural heart defects and sleep apnea, to name a few6. Research regarding the effects of chronic hypoxia on the human body is ongoing, and given its significance to those of us living at elevations of 9,000 feet and above, it is important to be aware of the impact our physical environment has on our health. Dr. Ebert-Santos is avidly involved in organizations dedicated to better understanding the health impacts of chronic hypoxia, and has several current research projects of her own that may help us to further understand the underlying science.

Kayla Gray is a medical student at Rocky Vista University in Parker, CO. She grew up in Breckenridge, CO, and spent her third year pediatric clinical rotation with Dr. Chris at Ebert Family Clinic. She plans to specialize in emergency medicine, and hopes to one day end up practicing again in a mountain community. She is an avid skier, backpacker, and traveler, and plans to incorporate global medicine into her future practice.

Citations

  1. Theodore, A. (2018). Oxygenation and mechanisms for hypoxemia. In G. Finlay (Ed.), UpToDate. Retrieved May 2, 2019, from https://www-uptodate-com.proxy.rvu.edu/ contents/oxygenation-and-mechanisms-of-hypoxemia?search=hypoxia&source=search_ result&selectedTitle=1~150&usage_type= default&display_rank=1#H467959
  2. Michiels C. (2004). Physiological and pathological responses to hypoxia. The American journal of pathology, 164(6), 1875–1882. doi:10.1016/S0002-9440(10)63747-9. Retrieved May 2, 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615763/ 
  3. Kolar, F. (2019). Molecular mechanism underlying the cardioprotective effects conferred by adaptation to chronic continuous and intermittent hypoxia. 7th Chronic Hypoxia Symposium Abstracts. pg 4. Retrieved May 2, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  4. Das, K., Biradar, M. (2019). Unilateral common carotid artery occlusion and brain histopathology in rats pre-conditioned with sub chronic hypoxia. 7th Chronic Hypoxia Symposium Abstracts. pg 5. Retrieved May 2, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  5. Gerstein, W. (2019). Endothelial dysfunction at high altitude. 7th Chronic Hypoxia Symposium Abstracts. pg 11. Retrieved May 7, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  6. Hypoxemia. Cleveland Clinic. Updated March 7, 2018. Retrieved May 9, 2019. https://my.clevelandclinic.org/health/diseases/17727-hypoxemia

Sleep at High Altitude

Have you thought of what it would be like living in the mountains year-round? Medical professionals find it is important to look at what living at high elevations can do to the human body. One activity heavily affected is sleep. As mentioned in previous blog posts, visitors often have trouble falling asleep, staying asleep, and feeling rested in the morning. A recent study published in Physiological Reports measured the effects of sleeping patterns at high elevation. The participants experienced a simulated elevation inside a hyperbaric chamber. This mimicked sleeping at elevations of 3000 meters (9,842 feet) and 4050 meters (13,287 ft) for one night and then sleeping at sea level for several nights to establish a baseline for the research participants. Participants exercised for 3 hours in the hyperbaric chamber allowing researchers to observe how the lower oxygen concentrations affected their ability to perform strenuous tasks. The group that slept in a simulated 4050 meter environment had an increased heart rate that was 28% higher and an oxygen saturation 15% lower than the 3000 meter participants. When comparing sleep itself, the group at 4050 meters had 50% more awakening events throughout each night. This goes along with previous research on this blog that states that people who sleep at high altitude complain of insomnia and frequent awakening when first arriving at high elevation.

These numbers increase even more dramatically when compared to participants at sea level. Related symptoms reported during this study showed the incidence of acute mountain sickness occurred in 10% of the participants at a simulated 3000 meters, increasing to 90% at 4050 meters. As mentioned, the average heart rate increases and oxygen saturation decreases as the elevation increases. The baseline heart rate at sea level was 62 beats per minute, increasing to 80 at 3000 meters and 93 at 4050 meters. Ideally health care providers aim to oxygenate vital organs by keeping the oxygen saturation level between 92-100%. The lower the oxygen level the harder it is to keep organs properly profused. Age, health status, and place of residence are taken into consideration when examining study reports. Oxygen saturation at sea level was 98% decreasing to 92% at 3000 meters and 84% at 4050 meters.

As mentioned in a previous post by Dr. Neale Lange, sleeping at high altitudes can be hard due to the frequent awakenings and nocturnal hypoxia caused by the low oxygen levels at higher elevation. This study reiterates these findings with the results of the average oxygen saturation at 3000 meters being around 92%. Dr. Lange also found that sleep apnea was often more prominent and had more negative effects on the human body in environments that were lower in oxygen. This study agrees with that statement finding that people with sleep apnea had twice the hourly awakenings compared to those at higher elevation that did not have sleep apnea. Dr. Lange also pointed out that the contribution of hypobaric atmosphere to symptoms at altitude as opposed to pure hypoxemia is unknown. Frisco, Colorado is at an elevation of 2800 meters. Ongoing research at Ebert Family Clinic including residents and visitors along with laboratory studies such as this one can guide decisions about interventions and treatment to improve sleep and help us enjoy our time in the mountains.

References

  1. Figueiredo PS, Sils IV, Staab JE, Fulco CS, Muza SR, Beidleman BA. Acute mountain sickness and sleep disturbances differentially influence cognition and mood during rapid ascent to 3000 and 4050 m. Physiological Reports. 2022;10(3). doi:10.14814/phy2.15175
  2. Blog post: HOW DO YOU DEFINE A GOOD NIGHT’S SLEEP?:AN INTRODUCTION TO THE SLEEPIMAGE RING, AN INTERVIEW WITH DR. NEALE LANGE

Casey Weibel is a 2nd year student at Drexel University, born and raised in Pittsburgh, Pennsylvania. He went to Gannon University for his undergrad and got a degree in biology.  Before PA school, Casey was an EMT.  He enjoys hiking and kayaking and is a big sports fan. 

How to Stay Healthy During Your Holidays at High Altitude

Acute Altitude Illness affects about 7.4% of travelers to mountain resort areas, including Frisco, Colorado which sits at an altitude of about 2800 meters. Dr. Kendrick Adnan, MD, MSPH is an emergency medicine physician associated with Vail Health. Dr. Adnan often sees visitors to Vail and other popular ski and vacation areas in Summit County that are experiencing Acute Altitude Illness. I sat down with Dr. Adnan, and we discussed the treatment of Acute Altitude Illness as well as signs, symptoms, risk factors, and prevention of Acute Altitude Illness.

What causes Acute Altitude Illness?

  • Acute Altitude Illness develops when the body responds to hypoxia, a low level of oxygen in the blood. Areas of high altitude have a lower concentration of oxygen in the air than lower altitudes, which makes your body work harder to put oxygen in your blood. Your body responds to the lower oxygen concentration by increasing how often and how deeply you breathe. This causes a decrease in carbon dioxide and increase in tpH in the blood. Your heart, lungs, blood vessels, and kidneys all respond to the low pH in your blood, which can cause the signs and symptoms of Acute Altitude Illness.
  • Some people will experience severe forms of Acute Altitude Illness called High-Altitude Pulmonary Edema or High-Altitude Cerebral Edema. These are life-threatening conditions that can cause death in both adults and children if not treated promptly by a medical professional.

What are the signs and symptoms of Acute Altitude Illness in adults?

  • Headache
  • Nausea
  • Vomiting
  • Decreased appetite
  • Fatigue
  • Shortness of breath on exertion
  • Decreased exercise tolerance
  • Chest tightness
  • Hypoxia

What are the signs and symptoms of Acute Altitude Illness in children?

  • Fussiness
  • Poor feeding
  • Pale or blue-tinged skin
  • Sleeping too much or too little

What is the treatment for Acute Altitude Illness (AAI)?

The best treatment for AAI is supplemental oxygen through a nasal cannula and descent to a lower elevation. You will need to visit a healthcare provider, clinic, or hospital to get supplemental oxygen if your oxygen level drops below 89%. Visitors to high-altitude areas may be hesitant to abandon their vacation plans in order to descend to a lower altitude. A healthcare provider may be able to prescribe medications to help you recover from AAI. However, if your low oxygen level does not improve with supplemental oxygen and medication, it is important to descend to an area of lower altitude.

Studies show that acetazolamide, dexamethasone, and tadalafil are medications that can potentially treat Acute Altitude Illness and/or High-Altitude Pulmonary Edema. A healthcare provider may prescribe these medications for you if appropriate.

What increases the chance that I will experience Acute Altitude Illness?

  • Traveling by airplane from low altitude to high altitude.
  • Being a resident of low altitude
  • Past episode of Acute Altitude Illness
  • Physical exertion at high altitude, especially in colder temperatures

What can be done to prevent Acute Altitude Illness and High-Altitude Pulmonary Edema?

  • A slower ascent will decrease your risk of AAI. Dr. Adnan recommends spending the night in Denver after air travel if you are planning to visit a high-altitude area.
  • Avoid strenuous exercise like skiing, hiking, and mountain biking for 48-72 hours after arrival to a high-altitude area.
  • Buy a pulse oximeter to check your oxygen level. A level above 89% is normal at high-altitude and does not require treatment.
  • Ask your healthcare provider about taking Diamox (acetazolamide) for 2-3 days before you arrive at a high-altitude destination. You will need a prescription for this medication.
  • Avoid medications that decrease your respiratory rate like opiates, sleeping medications, benzodiazepines, and barbiturates.

References

Schafermeyer, R. W. DynaMed. Acute Altitude Illnesses. EBSCO Information Services. https://www.dynamed.com/condition/acute-altitude-illnesses. Accessed November 19, 2021. Simancas-Racines D, Arevalo-Rodriguez I, Osorio D, Franco JVA, Xu Y, Hidalgo R. Interventions for treating acute high altitude illness. Cochrane Database of Systematic Reviews 2018, Issue 6. Art. No.: CD009567. DOI: 10.1002/14651858.CD009567.pub2. Accessed 03 November 2021.

Sasha Scott is a physician assistant student at Drexel University in Philadelphia, PA. She is originally from Indianapolis, IN and attended Purdue University for undergrad. Sasha enjoys running, cross stitching, cooking, and exploring Philadelphia when she is not studying!

Carotid Body Tumors at High Altitude

Carotid body tumors (CBTs) are more common at higher altitudes. It also has been proposed that altitude can play a role in the genetic mutations that cause CBTs to form in the inherited types of CBTs. How might altitude affect the genetics of CBT formation?

The carotid body is a peripheral nervous system sense organ. It is located bilaterally at the bifurcation of the common carotid artery, between the internal and external carotid arteries. The carotid body helps maintain physiologic homeostasis with the help of its sensory chemoreceptors. These sensory chemoreceptors “detect changes in the quality in the composition of arterial blood flow, such as pH, CO2, temperature, and partial pressure of arterial oxygen” (Forbes & Menezes, 2021). The carotid body therefore responds to states of hypoxia, hypercapnia and acidosis.

Carotid body tumors (CBTs) are rare paragangliomas of the head and neck. Sporadic, familial and hyperplastic are the 3 different forms of CBTs.  The hyperplastic form is most prevalent in patients who are in chronic hypoxic states. Chronic hypoxic states are seen in patients with COPD or cyanotic heart disease. However, chronic hypoxic states are also seen in people who live at high altitude. The only known risk factors for developing a carotid body tumor include chronic hypoxia and genetic predisposition. The only treatment for CBTs is surgery, which is a very challenging surgery due to the complex location of CBTs by a main vessel, the carotid artery.

This is an image of an MRI showing carotid body tumors (Burgess et al., 2017)

Risk for CBT’s are related to different altitudes. Prasad et al. (2019) stated the prevalence of CBTs were increased at altitudes exceeding 2000 feet of above sea level where as Chaaban (2021) states CBTs are more common in people living at altitudes exceeding 5000 feet above sea level.  The big question becomes why are CBTs more prevalent at altitude? Forbes & Menezes (2021) found that the Carotid body plays a role in the acclimation to high altitude in regards to ventilation, respiratory rate and oxygen levels. At increasing altitudes, there is less oxygen in the air. This leads to a hypoxic state and causes the respiratory rate to increase. The Carotid body itself is responsible for detecting the low oxygen level at high altitude and then increasing the respiratory rate. There may be a chronic hypoxic state as acclimation to high altitude occurs. There also may be a defect in oxygen sensing by the carotid body, which worsened by moderately high altitudes (Astrom et al., 2003). Hyperplasia of the glomus cells of the Carotid body occurs due to the chronic hypoxia and cellular proliferation can occur due to the defect in oxygen sensing. Hyperplasia and cellular proliferation can then lead to tumor formation. It is even found that patients with multiple tumors, like having bilateral CBT’s (as pictured on the MRI imaging) at first time of diagnosis live at higher altitudes, with longer duration of high altitude residence. (Astrom et al., 2003).

CBTs are rare and some surgeons may only see a few CBTs in their career. According to two ENT surgeons in Lakewood, Colorado at a Level I Trauma center, they have encountered many more CBTs in Colorado in their career than in other places at lower altitude. Peter McGuire, MD has been practicing in Colorado for over 5 years as an ENT surgeon. He has encountered about 5-10 CBTs since being in Colorado (P. McGuire, MD, personal communication, November 9, 2021). He states he has only encountered two at lower altitude. When talking to Erin Roark, FNP, who practices alongside ENT surgeon Christopher Mawn, MD, in the 10 years they have been working together in Colorado they have encountered about 15-20 CBTs. (E. Roark, FNP, personal communication, November 10, 2021).

There is evidence that altitude can affect gene mutations. “It has been proposed that environmental hypoxia modulates genetic predisposition to CBP” (Praasad et al., 2019). It has been found that CBTs that develop at high altitudes have been associated with the penetrance, expressivity, and population genetics of what are considered inherited CBTs. Again, cellular proliferation can occur when there is a defect in oxygen sensing by the carotid body and this defect in oxygen sensing can be worsened by moderately high altitudes. This causes cellular proliferation, increased number of actively dividing cells and increased likelihood of an alteration of the DNA sequence (Astrom et al., 2003). An alteration of the DNA sequence is also called a second-hit somatic mutation. “Therefore, living at higher altitudes is expected to facilitate the development of independent tumor foci that develop clonally following the second-hit mutation” (Astrom et al., 2003).

Many questions remain regarding the increased prevalence of CBT’s at altitude. Research is needed to determine if an existent CBT grows when the patient moves from an area of low altitude to an area of high altitude. Genetic studies looking for underlying predispositions to these tumors and other conditions related to altitude will continue to be fundamental.

For more another article related to genetics and altitude see blog entry from December 2019 on aural atresia.

References

Astrom, K., Cohen, J. E., Willett-Brozick, J. E., Aston, C. E., & Baysal, B. E. (2003). Altitude is a phenotypic modifier in hereditary paraganglioma type 1: Evidence for an oxygen-sensing defect. Human Genetics, 113(3), pp. 228-237. https://doi.org/10.1007/s00439-003-0969-6.

Burgess, A., Calderon, M., Jafif-Cojab, M., Jorge, D., & Balanza, R. (2017). Bilateral carotid body tumor resection in a female patient. International Journal of Surgery Case Reports, 41, 387-391. https://doi.org/10.1016/j.ijscr.2017.11.019

Chaaban, M.R. (2021). Carotid body tumors. Medscape. Retrieved November 7, 2021 from https://emedicine.medscape.com/article/1575155-overview#a8.

Forbes, J. & Menezes, R. (2021). Anatomy, head and neck, carotid bodies. StatPearls Publishing. Retrieved November 7, 2021 from https://www.ncbi.nlm.nih.gov/books/NBK562237/.

Pacheco-Ojeda, L. A., MD. (2017). Carotid body tumors: Surgical experience in 215 cases. Journal of Cranio-Maxillo-Facial Surgery, 45(9), pp. 1472-1477. https://doi.org/10.1016/j.jcms.2017.06.007.

Prasad S., Paties C., Pantalone M., et al. (2019). Carotid body and vagal paragangliomas: Epidemiology, genetics, clinicopathological features, imaging, and surgical management. In: Mariani-Costantini R. (Ed.), Paraganglioma: A Multidisciplinary Approach (ch. 5). Brisbane (AU): Codon Publications. doi: 10.15586/paraganglioma.2019.ch5. Retrieved November 7th, 2021 from https://www.ncbi.nlm.nih.gov/books/NBK543230/.

Katelyn Guagenti is a FNP student at the University of Cincinnati. She graduates December 10, 2021. She lives in Lakewood, CO and she plans to work with Dr. Christopher Mawn and Dr. Peter McGuire at Aspen Ridge ENT clinic after graduation. In her free time she likes to do CrossFit, hike, ski, snowmobile, and any other activity that involves hanging out with her Husband, Vincent, and dog, Judd. Most of all she loves to go to Grand Lake, CO, her favorite place here in beautiful CO.