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Lightning Strikes in Colorado

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My love for hiking developed during my childhood explorations of the breathtaking landscapes of the Sierra Nevada. As I ventured into the rugged mountains and hiked along scenic trails, I couldn’t help but feel a deep connection with nature. However, my passion for hiking was not without its moments of caution. On several occasions, I witnessed the awe-inspiring yet intimidating power of lightning storms dancing across the vast mountain skies. These encounters instilled in me a profound curiosity about the risks associated with lightning strikes in high-altitude regions.

When I moved to Colorado for PA school, my awareness of the dangers posed by lightning strikes grew even stronger. The dramatic topography and frequent thunderstorms in Colorado amplify the risk for individuals exploring high-altitude areas. It was during my last clinical rotation at a burn unit that I had the opportunity to care for several patients who had been struck by lightning. Witnessing the effects firsthand fueled my determination to educate the public about the actionable steps they can take to stay safe during lightning storms.

Lightning strikes

​Lightning possesses an immense amount of energy, with a voltage of over 10 million volts (in comparison, most car batteries measure 12.6 V).1 Additionally, a lightning bolt reaches incredibly high temperatures, reportedly up to 30,000 Kelvin (53540.33 F).1 Lightning injuries occur in different ways, including as direct strikes, side splash, contact injuries, or ground current. 

Direct strikes are uncommon, accounting for only 5% of cases, and happen when a person is directly struck by lightning.2

Contact injuries occur when a person touches an object that is struck by lightning. 2

Side splash injuries occur when the current jumps or “splashes” from a nearby object and then follows the path of least resistance to reach the individual. These injuries make up about 1/3 of all lightning related injuries. 2

Ground current is the most prevalent cause of injury, accounting for half of all cases, and occurs when lightning strikes an object or the ground near a person and subsequently travels through the ground to reach the individual. 2

In Colorado, an average of 500,000 lightning flashes hit the ground each year. Based on data since 1980, lightning causes 2 fatalities and 12 injuries per year throughout the state.3According to data since 1980, lightning causes an average of 2 fatalities and 12 injuries annually throughout the state. 3 Colorado ranked third in the United States for the number of lightning fatalities between 2005 and 2014, as depicted in Figure 1.

Fig. 1. Lightning fatalities by state. 3

The high number of injuries attributed to lightning in Colorado can be influenced by several factors. One of these factors is the easy access to high elevation terrain, such as 14ers (mountains with a peak elevation of at least 14,000 feet). This accessibility allows inexperienced outdoor enthusiasts to venture into potentially dangerous situations due to their lack of knowledge and preparation.

For instance, individuals who are not familiar with summer weather patterns may embark on a hike above the tree line late in the day, underestimating the risk of a storm forming. This lack of understanding puts them in an exposed and perilous position should adverse weather conditions arise.

Even with thorough preparation and extensive knowledge of weather patterns, it is still possible to find oneself in a situation where you have to weather a storm. Given that a significant proportion of Colorado’s hiking trails are located above the tree line, where appropriate shelter is sparse, hikers are more susceptible to lightning strikes in these exposed areas. 

Pathophysiology of Lightning Strike Injuries

The overall ratio of lightning injuries to deaths is 10:1 and there is a 90% chance of sequelae in survivors.4 The primary mechanism of injury in lightning strikes is the passage of electrical current through the body. The high voltage and current can cause tissue damage through several mechanisms, including thermal injury, electrical burns, and mechanical disruption of tissues. The severity of the injury depends on factors such as the voltage and current of the lightning bolt, the duration of contact, and the pathway the current takes through the body.

Lightning strikes can cause various types of injuries, with cardiac and respiratory arrest being the most common fatal complications.5 The path of least resistance determines the flow of electricity through different organs in the body, with nerves being the most conductive, followed by blood, muscles, skin, fat, and bone. 5 When lightning strikes, the electrical surge can induce cardiac arrest and cessation of breathing by affecting the medullary respiratory center. As a result, most patients initially present with asystole and may progress to different types of arrhythmias, commonly ventricular fibrillation. 5

Interestingly, there have been case reports documenting successful resuscitation of lightning strike victims who were initially apneic and pulseless for as long as 15 to 30 minutes. 5This has led to the recommendation that in the immediate aftermath of a lightning strike, individuals who appear to be dead should be prioritized for treatment.

Superficial skin burns are experienced by around 90% of lightning strike victims, but deep burns are less common, occurring in less than 5% of cases. A characteristic skin manifestation of a lightning strike is the Lichtenberg figure, which is considered pathognomonic. Neurological symptoms can also occur, including keraunoparalysis, which is a transient paralysis affecting the lower limbs more than the upper limbs. This paralysis is often accompanied by sensory loss, paleness, vasoconstriction, and hypertension, and is thought to result from overstimulation of the autonomic nervous system, leading to vascular spasm. In most cases, this paralysis resolves within several hours, but in some instances, it may last up to 24 hours or cause permanent neurological damage. 5

Additionally, it is common for lightning strike victims to have a perforated tympanic membrane (eardrum) or develop cataracts immediately following the incident. These injuries to the ear and eyes are associated with the intense energy of the lightning discharge. 6

What can hikers do to stay safe?

Preparation

Monitor weather forecasts: Stay updated on weather conditions before engaging in outdoor activities, especially in areas prone to thunderstorms. Pay attention to thunderstorm warnings or watches issued by local authorities. Having a mobile or handheld NOAA Weather Radio All-Hazards (NWR) can also be helpful as it can transmit life-saving weather information at a moment’s notice. 

In Colorado most thunderstorms develop after 11 am, so it is best to plan your trip so that you are descending by late morning.7 Fig. 2 shows number of lightning fatalities by time of day in Colorado between 1980 and 2020. The vast majority take place after the 11 am threshold.

Fig. 2  Lightning fatalities in Colorado by time of day3

What to Do If Caught in a Storm

If you can hear thunder, you are close enough to be struck by lightning. Lightning can strike up to 25 miles away from the storm. 7 Once you hear thunder, if possible quickly move to a sturdy shelter (substantial building with electricity or plumbing or an enclosed, metal-topped vehicle with windows up). Avoid small shelters, such as picnic pavilions, tents, or sheds. Stay sheltered until at least 30 minutes after you hear the last clap of thunder.

Fig 3. Areas to avoid when sheltering from lightning.

If you are outdoors and cannot reach a suitable shelter, avoid open areas, hilltops, and high places that are more exposed to lightning strikes. Seek lower ground and stay away from tall objects, such as trees, poles, or metal structures. Bodies of water, including lakes, rivers, pools, and even wet ground, are conductive and increase the risk of a lightning strike. Move away from these areas during thunderstorms. Separate group members by at least 20 ft as lightning can jump up to 15 feet between objects.

​If a strike is eminent (static electricity causes hair or skin to stand on end, a smell of ozone is detected, a crackling sound is heard nearby), the current recommendation is to assume “lightning position”, pictured in Fig. 4.

Fig. 4. Lightning position8

To potentially reduce the risk of ground current injury from an imminent lightning strike, another strategy is to insulate oneself from the ground. This can be done by sitting on a pack or a rolled foam sleeping pad. However, it’s important to note that this and the lightning position should be considered a strategy of last resort and not relied upon as the primary means of prevention. Maintaining this position for an extended period can be challenging, and it’s crucial to prioritize seeking proper shelter and following established lightning safety guidelines to minimize the overall risk of injury. 5

Case Study

25 YO F presents to the Burn Unit as a transfer from Cheyenne Regional Medical Center s/p lighting strike. Patient (pt) was caught in a thunderstorm on a hike and sheltered under a tall tree. Suddenly, she felt like she was being lifted up into the air and then dropped. Pt had a brief (<5 sec) loss of consciousness (LOC). When she woke up, she was completely numb and couldn’t move any of her extremities. Witness (friend) states the lightning splashed from the tree to the pt. Pt denies hitting her head with the fall. She denies taking blood thinners. She has no past medical history (PMHx) or past surgical history (PSHx).

Physical exam 

Neuro: AOX4, No CN deficit on exam, LE paralysis resolved, LE paresthesia improving but still present

HEENT: L ruptured tympanic membrane, hearing loss on L side

CV: RRR

MSK: Soft compartments diffusely

Skin: Lichtenberg figures on bilateral LE 

Fig. 6. Lichtenberg figure on LLE

V/S: BP: 128/92, HR: 96, RR:18, SPO2: 98%, Temp 98.1F. 

CBC, CMP, troponin were all WNL. Serum hCG negative. CK mildly elevated (222) 

EKG showed NSR.

CXR, CT brain, and c-spine neg for acute injury

She was admitted to the UC Health burn center for observation with tele. Her lab work and vitals remained stable throughout her hospitalization. She was evaluated by the trauma team with a negative trauma work up. The day of discharge, she was tolerating a regular diet, ambulating and sating well on room air. She was deemed appropriate for discharge home without patient audiology and ophthalmology follow up. 

References

1. US Department of Commerce N. Understanding lightning science. National Weather Service. April 16, 2018. Accessed July 8, 2023. https://www.weather.gov/safety/lightning-science-overview. 

2. Cooper MA, Holle RL. Mechanisms of lightning injury should affect lightning safety messages. 21st International Lightning Detection Conference. April 19-20, 2010; Orlando, FL. 

3. US Department of Commerce N. Colorado Lightning statistics as compared to other states. National Weather Service. March 4, 2020. Accessed July 7, 2023.https://www.weather.gov/pub/Colorado_ltg_ranking. 

4. US Department of Commerce N. How dangerous is lightning? National Weather Service. March 12, 2019. Accessed July 8, 2023. https://www.weather.gov/safety/lightning-odds. 

5. Chris Davis, MD; Anna Engeln, MD; Eric L. Johnson, MD; Scott E. McIntosh, MD, MPH; Ken Zafren, MD; Arthur A. Islas, MD, MPH; Christopher McStay, MD; William R. Smith, MD; Tracy Cushing, MD, MPH. Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Lightning Injuries: 2014 Update. WILDERNESS & ENVIRONMENTAL MEDICINE. 2014; 25, S86–S95 

6. Flaherty G, Daly J. When lightning strikes: reducing the risk of injury to high-altitude trekkers during thunderstorms. Academic.oup.com. Accessed July 8, 2023. https://academic.oup.com/jtm/article/23/1/tav007/2635599. 

7. NWS Colorado Offices – Boulder G. Colorado Lightning Awareness Week june 19-25, 2022. ArcGIS StoryMaps. June 25, 2022. Accessed July 8, 2023. https://storymaps.arcgis.com/stories/11d021f1b800429a869ead2dc32c0f96. 

8. McKay B and K. How to survive A lightning strike: An illustrated guide. The Art of Manliness. April 25, 2022. Accessed July 8, 2023. https://www.artofmanliness.com/skills/outdoor-survival/how-to-survive-a-lightning-strike-an-illustrated-guide/. 

A woman with long, light brown hair over her shoulders wearing a blue, sleeveless shirt with red details smiles with blue eyes.

Sophia Ruef is a Physician Assistant student at Red Rocks Community College in Arvada, CO. She grew up on the central coast of California and earned her Bachelor of Science degree inBiology with a concentration in anatomy and physiology from Cal Poly San Luis Obispo. She worked as an EMT and a tech in the Bay Area after her undergraduate education. In her free time, she enjoys hiking, backpacking, canyoneering, and spending time with family and friends.

Acclimation, Altitude Science, Athletic Training, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Mountaineering

Mountain People Can Still Get Mountain Sickness: HL-HAPE, a Fourth Type of High Altitude Pulmonary Edema

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There are three types of High Altitude Pulmonary Edema (HAPE) recognized in visitors and people living at high altitudes. These include classic HAPE (C-HAPE), which involves an individual that lives at low altitude traveling to high altitude. Re-entry HAPE (RE-HAPE)  is seen in an individual that lives at high altitude who travels to low altitude and then returns to high altitude. And high-altitude resident pulmonary edema (HARPE) which occurs in an individual that lives at high altitude and does not change altitude (Ebert-Santos, Wiley). While these have been extensively studied and are subtypes that people are warned of, a fourth unexpected type of HAPE has been recently described by pediatric pulmonologist Santiago Ucros in Bogota, Columbia at the Universidad de los Andes. (Ucros)

Highlanders HAPE (HL-HAPE) occurs in people that live at high altitude who then travel to higher altitudes. Though most people who live at high altitudes for long periods of time assume they are immune to HAPE, the recognition of HL-HAPE shows this is not the case. One man had a run-in with HL-HAPE during his long-awaited trip to Mt. Kilimanjaro. 

A man wearing a neck gator under a grey baseball cap and dressed in cold-weather jacket and pants sits on a rock next to a tall giant groundsel plant with cushions of dead leaves puffing up heads of light-green leaves before the sloping of the mountain down into a valley with a white cloud floating above it.

A resident of Summit County, Colorado, Jonathan Huffman set out to climb Mt. Kilimanjaro with his wife Katie when he was 37 years old. He is originally from Texas, but has been living in Breckenridge, Colorado, elevation 9,600 ft, for 15 years. In preparation for the climb, he spent the summer hiking multiple fourteen thousand foot peaks in Colorado, trail running at 9,000-12,000 ft, and mountain biking. 

Two people stand smiling toward the camera with an arm around each other, dressed warmly in long pants, thick jackets and hats, one holding a water bottle, standing on an open field of high alpine shrubs with Mt. Kilimanjaro illuminated in the pink light of the sun, streaked with long, narrow clouds in the background

The elevation of Mt. Kilimanjaro is 19,341 feet and the summit generally takes each group anywhere from 5 to 9 days, depending on the route taken. In September, Jonathan and Katie traveled to Tanzania where they spent two days adjusting to jet lag and preparing for their climb. They had chosen to follow the Lemosho Route which is 42 miles long with an elevation gain of 16,000 to 17,000 feet. 

On the first day, Jonathan and his party started at the Lemosho trailhead (7,742 feet) and hiked up 9,498 feet to the first camp. He noticed that his throat felt dry and he found himself having to clear it often. He attributed this symptom to the dusty environment. 

On the second day, he felt as though his body was fighting the dust, which had found its way into his eyes, sinuses, and throat. He also felt extremely fatigued and stated that every action felt more difficult. Though he could tell his body was struggling to adapt, Jonathan continued to push forward with full force. He made it to the second camp at 11,500 feet. 

A group of orange and white panelled tents sit in the shade of a rocky mountain peak streaked with snow, illuminated in sun above the camp against a cloudless blue sky.

“Day three, we went from 11,500 feet to 13,800 feet,” Jonathan recounts. “After we arrived to this camp, our guides offered to allow us to take a break then hike even higher. This was [an] optional acclimatization test … but I actually skipped it. I was so tired when I got to camp on this day, I decided to just nap in the tent until dinner time.”

On the fourth day, Jonathan’s group hiked up an overpass to Lava Tower located at 15,190 feet. This was also an altitude test, and he passed. He stated that this was the highest he had ever climbed, but that he was beginning to feel more like his normal self. The group stopped for lunch at the tower, but he did not have much of an appetite. He ate the food anyways at the insistence of the guides. 

A sea of clouds illuminated in blues and soft pinks stretches out behind several tents pitched over a shaded, rocky mountain slope in the foreground.

“Then after lunch, we descended down to Barranco Camp [from 15,190 feet to 13,044 feet] and this is where I realized I had HAPE.”

As they were nearing the camp, he felt fluid building in his lungs that was easy to cough up. By the evening, however, he felt as though he was drowning and was unable to lay down. While the guides encouraged him to immediately hike down, he did not want to hike in the dark. He spent the night propped up on duffle bags or sitting in a kitchen chair, with his oxygen reaching as low as 67% at one point. 

Two people sit in the dark of a tent, one with an oxygen mask on and a red head lamp illuminating tin food containers and medical supplies in the foreground as he is administered oxygen.

In the morning, he received 30 minutes of oxygen treatment before beginning his 8-hour descent. His symptoms improved when he reached 6,500 feet. He was picked up in a rescue vehicle and received further treatment at a hospital in Moshi. While he made a full recovery, he stated that he still felt the effects of HAPE while exercising in Colorado at times, up to months after the experience. While Jonathan was only about 2 days away from the summit, he knew that turning back was the best choice. He plans to re-attempt the climb in a few years. 

Jonathan’s story serves as an important reminder to those living at altitude that HAPE can affect anyone. Jonathan’s wife Katie along with everyone else in the group also experienced mild symptoms of altitude sickness including headaches. Research still needs to be conducted on the cause and prevention of this condition in all types. While this shouldn’t stop hikers and climbers from climbing mountains, they should be aware of the signs and symptoms of HAPE, when to seek treatment, and the best ways to prevent it from occurring. 

A map of the Lemosho route as listed on the Ultimate Kilimanjaro guide site can be found here.

A group of people in bright colored pants, jackets and backpacks make their way down a red dirt trail surrounded by tall green grasses and trees extending over a white SUV with a red cross symbol on it in the background down the road.
A man in a beige baseball cap takes a selfie with three men in hats and jackets behind him smiling toward the camera with a white jeep labelled with a red cross in the background behind them.
Acclimation, Alcohol at Altitude, Altitude Science, Athletic Training, Backcountry, Backpacking, Child Growth & Development, Exposure, Health, High Altitude, High Altitude Training & Fitness, Huts, Hyperbaric Therapy, Medicine, Mountaineering, Naturopathic Medicine, Sleep at Altitude, Summit Huts

HAFE: High-Altitude Flatus Expulsion

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Often, at high altitude we hear complaints of gas pain and increased flatus in our infant population. Parents often wonder, are we doing something wrong? Is my child reacting to breastmilk, or showing an intolerance to certain foods?  Actually there is another explanation for increased flatus and gas pain in the high-altitude region of Colorado. 

The term HAFE was coined by Dr. Paul Auerbach and Dr. York Miller and published in the Western Journal of Medicine in 1981. Their discovery began In the summer of 1980, when the two doctors were hiking in the San Juan Mountains of Colorado on a quest to summit three 14ers. During their ascent they noticed that something didn’t smell right! As the pair continued to emit noxious fumes, they began to put their scientific brains to work and discovered HAFE. The symptoms include an increase in frequency and volume of flatus, or in other terms an increase in toots! We all have familiarity in watching our bag of potato chips blow up when reaching altitude or our water bottle expanding as we head into the mountains. This reaction is due to a decrease in barometric pressure. Based on Boyle’s law, decreased barometric pressure causes the intestinal gas volume to expand, thus causing HAFE (Skinner & Rawal, 2019).

A graphic illustrating how Boyle's law works: the pressure of a gas increases as its volume decreases.

To my surprise, a gas bubble the size of a walnut in Denver, Colorado (5280 ft) would be the size of a grapefruit in the mountain region of Summit County, CO (8000+ ft)! Trapped gas is known to lead to discomfort and pain. The use of simethicone may have merit in mitigating the effects of HAFE. Simethicone works by changing the surface tension of gas bubbles, allowing easier elimination of gas. This medication, while benign, can be found over the counter and does not appear to be absorbed by the GI tract (Ingold, C. J., & Akhondi, H., 2022). 

While this phenomenon may not be as debilitating as high-altitude pulmonary edema (HAPE), it deserves recognition, as it can cause a significant inconvenience and discomfort to those it inflicts. As the Radiolab podcast explained in their episode The Flight Before Christmas , expelled gas in a plane or car when driving up to the mountains can be embarrassing. While HAFE can be inconvenient, it is a benign condition and a matter of pressure changes rather than a disease or pathological process. We would love to talk more about HAFE at Ebert Family Clinic if you have any questions or concerns!

A bald eagle flies over a misty settled into the valley against the blue-green pine forest of a mountain.
A bald eagle flies toward its nest atop a bare lodgepole pine.

As always, stay happy, safe, and healthy 😊

Taylor Hollingsworth is finishing her final semester as a family nurse practitioner (FNP) student at Georgetown University. Originally from the east coast, Taylor plans to start her FNP career in North Carolina close to family. She has a passion for pediatric and family wellness and has worked as a pediatric intensive care unit nurse for 6 years! In her free time, Taylor loves to hike, fly fish, run, and spend time with her fiancé Logan. 

References

Auerbach, P. & Miller, Y. (1981). High altitude flatus expulsion. The Western Journal of Medicine, 134(2), 173-174.

Chemistry Learner. (2023). Boyle’s Law. https://www.chemistrylearner.com/boyles-law.html

Ingold, C. J., & Akhondi, H. (2022). Simethicone. StatPearls Publishing. 

McKnight, T. (2023). The Flight Before Christmas [Audio podcast]. Radiolab. https://radiolab.org/episodes/flight-christmas

Skinner, R. B., & Rawal, A. R. (2019). EMS flight barotrauma. StatPearls Publishing. 

Acclimation, Altitude Science, Backpacking, Child Growth & Development, Doc Talk, Exposure, Genetics, Health, High Altitude, High Altitude Training & Fitness, Medicine

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

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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.

Acclimation, Altitude Science, Exposure, Genetics, Health, High Altitude, Sleep at Altitude

Are Epigenetics the Bridge to Permanent Physiologic Adaptations in Organisms Living at High Altitude?

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Epigenetics slide from speaker at Hypoxia conference in La Paz Bolivia, 2022

The CDC defines epigenetics as “the study of how your behaviors and environment can cause changes that affect the way your genes work… epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a sequence.”1 Examples of epigenetic changes include methylation, histone modifications, and non-coding RNAs. Researchers have postulated the involvement of epigenetics in an organism’s adaptations to hypoxic high-altitude environments. After looking into this topic, I questioned if epigenetics may be the bridge to the permanent physiologic alterations in organisms living at high altitudes. 

Hypoxia Inducible Factor-1 (HIF-1) is a nuclear transcription factor activated in hypoxia states, and regulates several oxygen-related genes. The role of epigenetics, specifically methylation of HIF-1 in the expression of the erythropoietin gene, in states of hypoxia was researched. Erythropoietin was chosen due to it being a widely known protein that stimulates erythropoiesis in states of hypoxia. It was confirmed that HIF-1 binds to a HIF-1 binding site (HBS) on the erythropoietin enhancer and will induce transcription of erythropoietin.2 CpG methylation in the HBS interferes with HIF-1 binding, thus inhibiting the activation of transcription of erythropoietin.2  They also found that there were several other oxygen-related genes that were susceptible to similar epigenetic changes.2 Another study investigating HIF-1 and its binding to HIF-1 response element (HRE) upstream to a target gene confirmed the potential for epigenetic changes, specifically methylation. They found that this HIF-1 binding site has a CpG dinucleotide, making it inherently susceptible to methylation.3 To clarify, the most notable epigenetic change is the methylation of cytosine located 5’ to guanine, known as CpG dinucleotides.3 Again, they reported that methylation of the CpG island in the HIF-1 binding site upstream of the target gene, erythropoietin, was negatively correlated with its expression.3 

Furthermore, research on epigenetic changes in rats exposed to long and short-term intermittent hypoxic environments and their room air recovery treatments suggests there is a long-term effect in rats exposed to long-term intermittent hypoxia.4  Rats were exposed to short-term (10 days) and long-term (30 days) intermittent hypoxia resembling obstructive sleep apnea oxygen profiles.4 The short-term hypoxic rats treated for 10 days at room air reversed their altered carotid body reflexes including hypertension, irregular breathing, and increased sympathetic tone. While the long-term hypoxia rats treated for 30 days at room air did not have a reversal of altered carotid body reflexes.4 There were similar results in reactive oxygen species (ROS) and antioxidant enzyme (AOE) levels. The long-term hypoxia rats had increased levels of ROS and decreased AOEs in their recovery periods compared to the short-term hypoxia rats.4 

Erythropoietin is not the only oxygen-related gene that is affected. For example, a study looked at the methylation profiles of Tibetan and Yorkshire pigs under high-altitude hypoxia. IGF1R and AKT3 were two notable differentially methylated genes found to have high expression and low methylation levels in Tibetan pigs that suggest a role in adaptation to hypoxic environments.5 Both genes are responsible for cell proliferation and survival.5 Tibetan pigs are known to have become physiologically adapted to their high-altitude hypoxic environment over generations and epigenetic changes were verified in the genome-wide sequence ran in this study.5 This study alludes that epigenetics is not only a bridge but may be a part of the permanent physiologically selected adaptations to ensure survival at high altitudes.

In conclusion, research demonstrates a variety of epigenetic changes that are taking place in these high-altitude hypoxic environments. The research suggests that they may likely be tissue-specific as well. There are definite knowledge gaps in the exact roles that epigenetics may play in hypoxic environments and gene expression. There is room for more research and identifying alterations to epigenetics to improve human physiologic adaptations to hypoxia. 

References 

1. Centers for Disease Control and Prevention. What is Epigenetics. https://www.cdc.gov/genomics/disease/epigenetics.htm. Accessed December 30th, 2022.

2. Wenger, R.H., Kvietikova, I., Rolfs, A., Camenisch, G. and Gassmann, M. (1998), Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation-free hypoxia-inducible factor-1 DNA-binding site. European Journal of Biochemistry, 253: 771-777. https://doi.org/10.1046/j.1432-1327.1998.2530771.x

3. Yin H, Blanchard KL. DNA methylation represses the expression of the human erythropoietin gene by two different mechanisms [published correction appears in Blood 2000 Feb 15;95(4):1137]. Blood. 2000;95(1):111-119.

4. Nanduri J, Semenza GL, Prabhakar NR. Epigenetic changes by DNA methylation in chronic and intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol. 2017;313(6):L1096-L1100. doi:10.1152/ajplung.00325.2017

5. Zhang B, Ban D, Gou X, et al. Genome-wide DNA methylation profiles in Tibetan and Yorkshire pigs under high-altitude hypoxia. J Anim Sci Biotechnol. 2019;10:25. Published 2019 Feb 5. doi:10.1186/s40104-019-0316-y

A woman in a white coat with long, dark, straight hair below her shoulders smiles.

Emily Paz is a third-year medical student at Rocky Vista University College of Osteopathic Medicine and is looking forward to pursuing a career in orthopedics. She is from the central coast of California and earned her Bachelor of Science degree in General Biology from the University of California San Diego. She worked in an emergency department as an EMT after her undergraduate education which reaffirmed her passion and curiosity for medicine. In her free time, she enjoys snowboarding, practicing Muay Thai, cooking, and spending time with family and friends.

Acclimation, Altitude Science, Athletic Training, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Mountaineering

When Altitude gets High, does Stroke get higher?

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Does altitude increase or decrease risk of strokes? As one review put it, “Due to limited literature, lack of large series, and controlled studies, the understanding of stroke at high altitude is still sketchy and incomplete”. What is clear is that stroke at high altitude can often be misdiagnosed (or underdiagnosed), due to the similarity of initial presentation with high altitude cerebral edema (HACE). Both conditions present with imbalance or ataxia, and both can present with focal neurological deficits.  There are few large urban populations at high altitude (Addis Ababa in Ethiopia is 7,726 ft), so medical providers have fewer resources.  Without the ability to perform neuroimaging with a CT scan or MRI in a timely manner a diagnosis of HACE vs. stroke could be uncertain. HACE often causes global cerebral dysfunction, differentiating it from an early stroke before the onset of focal symptoms can and often does prove challenging. 

While the prevalence of strictly hemorrhagic and ischemic strokes at high altitude remains murky, it is known that exposure to high altitude can result in conditions such as TIA, cerebral venous thrombosis (CVT), seizures, and cranial nerve palsies. Most of the research that has been done on strokes is focused on “moderate” and “high” altitudes, as opposed to “very high” or “extremely high” altitudes. As such, there is very little research on populations living at 3500m or higher. There was at least one tangible piece of evidence indicating that the higher the elevation, the earlier the mean onset of stroke – Dhiman et al. (2018) found that at an elevation of 2,000m, the mean age of onset of stroke was 62 years. The age decreased to a mean of 57.9 years at 2,200m in another study (Mahajan et al. (2004)). Yet another study (Razdan et al. (1989)) found 10.9% of the patients in their sample suffered strokes aged < 40, though this was at an altitude of only 1,530m. Some reports suggest higher stroke prevalence at higher altitudes, and at a strikingly young age – between age 20 and age 45.

Student presentation on stroke at altitude at Colorado Medical Society meeting 2022

There have been mixed results on the effect that altitude has on strokes. One systematic review study found 10 studies displaying an increase in stroke prevalence with higher altitude, 5 other studies showing that altitude was actually protective against stroke, and 2 studies in which the results were ambiguous. This study and other sources alluded to the fact that poorer stroke outcomes at higher altitude may be due to polycythemia and increased viscosity of blood. Specifically, Ortiz-Prado et. al noted that “living in high-altitude regions (>2500m) increases the risk of developing thrombosis through hypoxia-driven polycythaemia which leads to a hypercoagulation unbalance”, which was associated with increased risk for stroke. Ortiz-Prado et. al noted that most of their info came from “very few cross-sectional analyses”. These analyses did find “a significant association between living in high-altitude regions and having a greater risk of developing stroke, especially among younger populations”. When the effects of altitude on stroke were broken down by race (Gerken, Huber, Barron, & Zapata, 2022) it was found to be protective in some populations (Whites, African Americans), but detrimental in other populations (Hispanics, Asian-Pacific, and American-Indian). Going back to the work of Ortiz-Prado et. al, altitude increased the risk of stroke at elevations above 3500m, when the time spent at this elevation was at least 28 days, and more so in younger persons (below the age of 45). At lower elevations, between 1500m and 3500m, increased / easier acclimatization and adaptation to hypoxia seemed to offer protective effects against the risk of stroke. Chronic exposure to hypoxia at high altitude triggers adaptive / compensatory mechanisms, such as higher pulmonary arterial flow and improved oxygen diffusing capacity. Ortiz-Prado et. al concluded that a window of ideal elevation seems to exist – below an altitude of 2000m the adaptive mechanisms do not seem to be sufficient to yield a protective effect – however, above 3500m, adaptive mechanisms may actually become maladaptive (excessive polycythemia & blood stasis), yielding a higher risk for stroke. A lack of any adaptation (i.e. in altitude naïve persons) was even more detrimental at such high altitudes, with the authors concluding that “above 3500–4000m, the risk of developing stroke increases, especially if the exposure is acute among non-adapted populations” (Ortiz-Prado et. al, 2022).

Strokes are more common in males compared to females, and this held true at altitudes of 3380m, 4000m, and 4572m. In addition to the standard vascular risk factors such as hypertension, smoking, and diabetes, the higher incidence of polycythemia in persons living at high altitude is thought to play a role. One study (Jha et al. (2002)) found that 75% of the patients in their sample who had suffered strokes had some form of polycythemia – this was at an altitude of 4270m. (Dr. Christine Ebert-Santos of Ebert Family Clinic in Frisco, Colorado at 2743m suspects everyone who lives at altitude has polyerythrocythemia as more accurately described by Dr. Gustavo Zubieta-Calleja of La Paz, Bolivia at 3625m.)

Only about 2% of the world’s population resides at what is considered “high altitude”. Given the current world population (over 8 billion, 5 million), that is still over 160,100,000 people. The sheer number of people that may be at increased risk of stroke is all the more reason for us to act, and act soon, to get more research done. This is further exemplified by the fact that “cerebrovascular events or stroke is the second leading cause of death worldwide, affecting more than 16 million people each year” (Ortiz-Prado et. al). Guidelines need to be implemented to assist in the diagnosis and treatment of stroke at high altitude, to help differentiate it from related conditions such as HACE, giving patients the standard of care that they need and deserve. While a fascinating topic, stroke seems to be delegated to the sidelines in the mountains, cast aside by culprits such as HAPE, HACE, altitude sickness, and hypoxia. More research, more resources, and more funding need to be funneled into understanding stroke at higher altitudes. Overall, it is clear living at or even exposure to higher altitudes can result in a multitude of neurological symptoms, and that a higher incidence of stroke may yet be one of them.

References

Maryam J. Syed, Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at Moderate and High Altitude. High Altitude Medicine & Biology.Mar 2022.1-7. http://doi.org.mwu.idm.oclc.org/10.1089/ham.2021.0043

Current World Population – https://www.worldometers.info/world-population/ 

Ortiz-Prado E, Cordovez SP, Vasconez E, Viscor G, Roderick P. Chronic high-altitude exposure and the epidemiology of ischaemic stroke: a systematic review. BMJ Open. 2022;12(4):e051777. Published 2022 Apr 29. doi:10.1136/bmjopen-2021-051777

Gerken, Jacob (MS), Huber, Nathan (MS), Barron, Ileana (MD, MPH-S), Zapata, Isain (PhD). “Influence of Elevation of Stroke and Cardiovascular Outcomes”. Poster presented at a conference in Colorado, in 2022.

Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058702/ https://www-liebertpub-com.mwu.idm.oclc.org/doi/full/10.1089/ham.2021.0043

Born in Salt Lake City, Utah, Piotr Poczwardowski has also lived in Upstate New York, Florida, and Colorado (where he spent the 13 years prior to moving to Glendale for PA school). While attending the University of Denver, he volunteered at a nearby hospital Emergency Department, and also participated in a study abroad program in Italy. After earning a degree in Psychology, he worked as both a Primary Care Medical Scribe and Neurology MA. His main hobbies include skiing, watching movies, hiking, swimming, playing video games, reading, and playing ping pong. Piotr has also volunteered at the Sky Ridge Medical Center Emergency Department and secured a job as a Primary Care Medical Scribe after graduating from the University of Denver in 2018. Piotr is now attending Midwestern University’s PA program in Glendale, AZ.

Acclimation, Altitude Science, Athletic Training, Child Growth & Development, Doc Talk, Exposure, Health, High Altitude, High Altitude Training & Fitness, Medicine, Mountaineering

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

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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 previous 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, Re-entry HAPE in High Altitude Residents.

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.  The University of Heidelberg recently published an article on the genetics of pulmonary hypertension (HARPE is the New HAPE) and is interested in testing families here who have had more than one person affected by HAPE.

Exposure, Health, High Altitude

Exostosis of the External Auditory Canal – Surfer’s Ear

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You do not have to be a surfer to have surfer’s ear, but what is it exactly?

Not to be confused with swimmer’s ear surfer’s ear or exostosis of the ear auditory canal is when there is the presence of multiple benign boney outgrowths. It is quite common in individuals who have repeated exposure to cold water or wind, which typically ends up being those who surf waves in the pacific.

So now that we know what surfer’s ear is, how can we tell if we have it?

The diagnosis of Surfer’s ear is made by visual exam with an otoscope by a medical provider. Generally, there are no symptoms of Surfer’s ear unless there are multiple bony outgrowths, or the ones present are occluding your ear canal. In those cases, you may experience ear infections as these outgrowths can narrow the ear canal causing water and debris to become trapped and cause an infection. When there is significant occlusion of the ear canal typically 90% or more conductive hearing loss may occur.

What is the treatment for surfer’s ear?

A great preventative tool, to decrease the occurrence of these bony outgrowths is to wear ear protection like ear plugs when you have exposure to cold water or earmuffs when exposed to cold winds. As mentioned above, when there is only a few and/or small boney outgrowths there tends to be no associated symptoms and in those cases no need for treatment. In those, however, that continue to have exposure to cold water/winds, have several boney outgrowths and/or significant occlusion the only definitive treatment is to have those bony outgrowths removed surgically, this is typically done by an Ear, Nose, and Throat specialist.

References

  1. Surfer’s ear. UCI Health Otolaryngology. https://www.ucihealth.org/medical-services/ear-nose-throat-ent/hearing-ear-disorders/surfers-ear. Accessed October 11, 2022.
  2. Weber PC. Etiology of Hearing Loss in Adults. UpToDate. https://www.uptodate.com/contents/etiology-of-hearing-loss-in-adults?search=surfers+ear§ionRank=1&usage_type=default&anchor=H9&source=machineLearning&selectedTitle=1~150&display_rank=1#H9. Published March 15, 2022. Accessed October 11, 2022.
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Gabriela Rodriguez Ortega is a second year Physician Assistant student at Red Rocks Community College in Arvada, CO. She grew up in South Florida and received a Bachelor of Science in Biomedical Sciences and Bachelor of Arts in Psychology from the University of South Florida (Go Bulls!). Prior to PA school, she held many positions in the medical field including ENT medical assistant/scribe, pharmacy technician and ER medical scribe. In her free time, she enjoys spending time with family and friends, running, hiking, roller skating and playing guitar.   

Acclimation, Altitude Science, Child Growth & Development, Doc Talk, Exposure, Health, High Altitude, Medicine

HARPE is the New HAPE

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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.

Acclimation, Altitude Science, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Medicine, Mountaineering, Technology

High-Altitude Pulmonary Edema is not just for tourists

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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/