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.
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/
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.
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.
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.
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
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.
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.
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
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
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/
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
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
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
Hypoxemia. Cleveland Clinic. Updated March 7, 2018. Retrieved May 9, 2019. https://my.clevelandclinic.org/health/diseases/17727-hypoxemia
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
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
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.
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 (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
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.
The nuances of wound healing at high altitude is a topic that has already been explored on this platform (see Eric Meiklejohn’s “Wound Care at Altitude”). Identifying the impact that impaired oxygen delivery can have on healing time, tissue regeneration, and infection rates offers great insight into the roles health care providers can assume to support our high-altitude patients. For this interview, I was able to speak directly with a Summit County resident who had firsthand experience with these processes.
I’ve heard a bit about your experiences with wound healing at high altitudes I will ask some preliminary questions,. This entire experience was more of a marathon than a sprint. How long have you been living at this altitude, and how old were you at the time of your procedure? I’d lived at high altitude for over twenty-six years before I was diagnosed with breast cancer. I was Fifty-three when I had my surgery. I was in great shape, exercising regularly, and eating really well.
Tell me about your procedure: Well, the initial procedure was in January 2018 down in Denver. I had a bilateral mastectomy done to remove the cancerous tissue, and bilateral expanders were inserted during that surgery so that down the line I could have implants placed. Within the first week we started noticing some necrotic changes to my incisions, and that they were not healing well. The expanders were inflated with air, and it was thought that my traveling back to high altitude from Denver could have increased the pressure inside them. By the end of week one I went back in to see my doctor, who deflated my expanders pretty significantly.
Have you ever been diagnosed with a medical condition that could affect wound healing, such as Diabetes or Hypertension? No. Breast Cancer was my first real medical diagnosis.
Had you ever had surgery while living at this altitude before? And if so, what was the outcome? Yes, I’d had surgery for an umbilical hernia and that went very well. No complications at all, everything healed just fine. I’d also had tendon damage in my right hand after a fall, and I recovered really well after that surgery at this same altitude.
Regarding healing after your mastectomies, describe the anticipated wound healing time and wound care directions. The time estimate for recovery was four weeks. I was to rest for two weeks, increase activity slightly for the second two weeks with minimal physical therapy, then by the end of that fourth week the projection was that I would be mostly recovered. I was given strict precautions against heavy lifting, restricting arm movements, and not driving. For wound care I was doing daily dressing changes, not submerging the area in water, and applying Silvadene cream twice daily.
Following the removal of the expanders, what was the rest of the healing process like? Over the next two months I cared for my wounds at home. They were open and oozing, and over time the daily dressing changes and medication applications became quite taxing, both physically and emotionally. It took a lot out of me, and really interfered with my day-to-day life…not to mention the pain. On March 9th, 2018 I underwent an incision revision and resection procedure for the necrotic tissue. At that point my breast tissue had manifested itself as far as which parts were healthy and which would die, so they went in and resected the areas that were not viable. On the left side I lost most of the top surface of the breast, including the entire nipple area. Two weeks after that, I had a [chemo therapy] port placed in my arm so I could begin treatments, but that incision also had a difficult time healing. That eventually led to a one month delay in my chemo therapy.
In March and April the incisions on the right breast eventually healed, but because of all the tissue loss and necrosis on the left side those wounds did not heal. There was still a lot of drainage from that breast and it was mostly still open so I had to keep the bandage on. By early May (after this wound had been open for 5 straight months) my doctor and I started seeing more signs of infection to that breast, so around May 12th of 2018 he called me in for an emergency procedure and I had the expander completely removed from my left breast. I continued chemo and eventually that left side began to heal in the absence of the expander.
During this time, from March until I finished chemo in August, the port site never healed. The whole reason behind having the port placed was so it could heal over and I could go back to a normal life between chemo sessions. But instead I walked around with a bandage for those six months because my port site remained open. I had Her2 positive cancer, so after my six months of chemo I needed to continue taking Herceptin for one additional year. I opted to have the port removed after six months and had an IV placed every three weeks for my treatments. It was very hard on my veins, but I felt I had no choice.
In late August, with the port out and the left expander out, the last of my open wounds really started healing. I started looking at what I could do to help my tissue heal even better- my thought was that when this is all done and I am all well healed I would like to have my expanders placed and inflated again, but I don’t want to have to go backwards through this process. I did all this research, and that’s where I learned about hyperbaric therapy. That changed everything for me.
What did you learn about Hyperbaric therapy, and what was your experience with it? I did a lot of independent research online and came up with two options that I wanted to discuss with my doctor. The first was a topical option for applying oxygen directly to the wound, which was a very complicated and involved process -and the second was hyperbaric therapy.
I discussed this with my oncologist who was very familiar with hyperbaric chamber treatment centers in Denver, and who wrote me a referral to be evaluated at the one in Presbyterian St. Luke’s Medical Center. I was evaluated by their team, showed them all the photos I had been taking throughout this entire ordeal, and they seemed hopeful that they would be able to help me. I really wish I’d gone there sooner.
My plan was to use this to help me recuperate a little bit so I could give the expander one more shot on the left side. After having the left expander placed, the second phase of my plan was to get another course of hyperbaric therapy to aid in recovering from that procedure. It was eventually prescribed and accepted by insurance, who approved 27 hyperbaric sessions following my surgery.
I underwent the left expander placement in February of 2019, observed the same restrictions, and had identical at-home wound care as my initial surgery in January 2018, but with the addition of hyperbaric therapy my results were night and day. The day after surgery I started hyperbaric, and in so much less pain. I was off all pain medications within 48hours. I was able to get out, walk, function in my daily life, and the tissue healed really well. It was amazing! I felt great, had tons of energy, and it was just a completely different experience. It was nothing short of miraculous.
What was your hyperbaric chamber treatment like? It was five days a week in Denver. Being there was for me a huge learning experience. There were people there being treated for diabetic wounds, hearing loss, adjunct therapy for various types of cancer, joint and tendon disease, tissue necrosis, concussions, head trauma, and so many other things. I hadn’t known that this therapy could be utilized in all these different areas.
After your successful left expander placement, how was your transition to breast implants? Months after the left expander was reinserted, I did transition to breast implants (summer 2019) but even then, I insisted on post operative hyperbaric therapy. I was only approved for ten sessions that time, but the results were the same. Rapid healing time, noticeable decrease in pain after starting therapy, and the ability to function throughout the day. Of all the factors that played a role in this process for you, what variable would you most want to adjust? Honestly, I just wish I’d started hyperbaric therapy sooner. If there was a way to get providers who work with high altitude dwellers to recommend hyperbaric treatment as a part of their primary or secondary treatment course, that’s the one thing I would change.Well, I am very happy to know that despite the difficulty you experienced in this process, you are now three years post op, well healed, and satisfied with your results. Thank you again for sharing your story. My pleasure. If my sharing can help someone else find hyperbaric therapy or open them up to alternative methods of treatment sooner so as not to have to experience what I went through in those first few months, then it was all worth it.
Janell Malcolm is a second year Physician Assistant student in the Red Rocks PA Program in Arvada, Co. A Jamaica native, she loves the ocean, tropical fruit, and 100 degree weather. You will likely find her spending her free time with family or reading/re-reading Jane Eyre. Her personal and career goals are geared towards providing adequate medical care to underserved communities. Special interests post graduation: Labor & Delivery, General Surgery.
The Nobel prizes are announced this month. Alfred Nobel invented dynamite in 1866. Within 30 years, Nobel made a large fortune from his invention. He demonstrated his passion for literature and science by creating a yearly prize to discoveries most beneficial to humankind. The five prize categories include physics, chemistry, medicine (physiology), literature and peace. The Nobel prize nominations are made by university professors, national assemblies, state governments, and international courts. The prize is awarded yearly to individuals who have discovered a new paradigm or a paradigm shift within their field. The prize recipients are declared on the first Monday of October of every year and the award is presented by the Nobel assembly on November 10th, the anniversary of Alfred Nobel’s death. The Nobel prize consists of a gold medal, a diploma of recognition of achievement, and a cash prize in the amount of $1 million U.S. dollars.
There is no limit to the number of nominations that can be made or the number of times that an individual can be nominated. There were 400 candidates nominated in the field of medicine in 2019, all of which inspired, challenged, and demonstrated greatness in their field. In 2019 the Nobel Prize in Medicine honored three scientists for their discovery of the human body’s ability to adapt to low oxygen environments.
Hypoxia is a state of which oxygen supply is insufficient for normal life functions, experienced by the human body at high altitude. Tissues and cells require a range of oxygen in order to survive. Oxygen is required by mitochondria, in all cells, to convert food into useable energy. “Otto Warburg, the recipient of the 1931 Nobel Prize in Physiology or Medicine, revealed that this conversion is an enzymatic process.” At low oxygen environments, as experienced at high altitude, the body must adapt in order to maintain basic cellular function. There are several mechanisms in the human body that increase oxygen concentration including breathing rate, regulated by the carotid body, increased heart rate, stimulated by the vagus nerve, and increased production of red blood cells (RBCs) through the bone marrow, regulated by the kidney.
The carotid body is a chemoreceptor near the carotid artery that detects oxygen, carbon dioxide and pH levels in the blood. At low oxygen, the carotid body relays an afferent (ingoing) signal to the the brain via the glossopharyngeal nerve. The medullary center in the brain then sends an efferent (outgoing) signal that increases the respiratory rate to maximize oxygen delivery to the brain. The carotid sinus is a baroreceptor near the aorta of the heart which senses changes in pressure. As pressure increases in the atmosphere, experienced at high altitude, the carotid sinus sends a signal along the vagus nerve to the brain which then increases the heart rate. “The 1938 Nobel Prize in Physiology or Medicine was awarded to Corneille Heymans for discoveries showing how blood oxygen sensing via the carotid body controls our respiratory rate by communicating directly with the brain.”
At low oxygen environments, the kidney increases production of erythropoietin, which stimulates RBC generation in the bone marrow, called erythropoiesis, resulting in higher oxygen delivery to the brain and skeletal muscles needed at high altitude. Erythropoiesis was discovered in the early 20th century, however oxygen’s role in the process was not completely understood. The cell’s ability to sense and adapt to oxygen availability was discovered and explained by three scientists, William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza.
2019 Nobel Prize, Physiology:
Thanks to the work of Dr. Gregg L. Semenza and Sir Peter J. Ratcliffe, we now understand that the oxygen sensing mechanism that stimulates erythropoieten is present in all tissues, not just the kidney. Semenza conducted research on liver cells using gene-modified mice and found that a specific protein binds to an individual gene (the EPO gene), dependent upon oxygen availability. Semenza named the binding protein the Hypoxia-Inducible-Factor (HIF). The HIF protein was found to compose two transcription factors, HIF-1alpha and ARNT. In 1995, Semenza published his findings of the HIF protein. His work explained that when the body is at high oxygen environments, there is very little HIF-1alpha present within cells. At high oxygen availability, HIF-1alpha is rapidly degraded by a proteasome within cells. The degradation is signaled by a protein called ubiquitin which binds to HIF-1alpha at high oxygen, flagging HIF-1alpha for degradation by the proteasome. This process was recognized by the 2004 Nobel Prize in Chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose.
The mechanism by which ubiquitin binds, causing the degradation of HIF-1alpha at high oxygen environments was explained by the work of William Kaelin, Jr. who conducted research on von Hippel-Lidau’s (VHL) disease. The VHL gene mutation causes an increased risk of cancer. Kaelin showed that the VHL gene encodes a protein that prevents the onset of cancer and was involved in controlling responses to hypoxia. VHL is part of a complex that labels proteins with ubiquitin. Ratcliffe discovered the physical interaction of the VHL gene with HIF-1alpha, causing degradation of the HIF-1alpha at normal oxygen levels.
At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).
At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).
Kaelin and Ratcliffe’s research identified how oxygen levels regulate the interaction between VHL and HIF-1alpha. Their work demonstrated that at normal oxygen levels, hydroxyl groups are added to specific positions within HIF-1alpha, causing modification of the protein and allowing VHL to recognize and bind to HIF-1alpha, leading to degradation of the protein complex. At high altitude, cells produce a greater amount of the HIF-1alpha protein which binds to the EPO gene, up-regulating the production of erythropoietin hormone, stimulating RBC production. Together, Semenza, Kaelin, and Ratcliffe explained the oxygen sensing mechanism.
