Category Archives: Genetics

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Unveiling the Hidden Risks of Living at High Altitude on our Kidney Health, and What it Might Mean for Your Child

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The hallmark concern for the body living at high altitude is low oxygen. We breathe in less, and thus less is sent throughout our blood stream to our tissues. We are quick to think about how this affects our heart and lungs, but what about our kidneys? What are our kidneys even responsible for?

Kidneys filter, reabsorb, and excrete our blood in the form of urine. They connect our cardiovascular system with our genitourinary system. The flow through the kidneys also helps monitor and adjust our blood pressure. Their importance is truly undervalued. When they receive less oxygen than preferred (hypoxia), they will become injured. Specifically, the glomerulus (term for the filter) will become affected. When this happens, it is not efficient at filtration, and protein will spill out into our urine (proteinuria), a key feature of High Altitude Renal Syndrome (HARS).

Zooming further in below

And even further…

Another issue involves uric acid, the chemical at fault for causing gout. Due to the filter injury sustained from low oxygen, uric acid excretion is affected. It can thus build up in our musculoskeletal system and other tissues. It is famous for causing red, swollen, and painful joints. The enzyme that helps create uric acid (xanthine oxidase) is also turned on by reactive oxygen species during hypoxia. This then causes further uric acid crystal deposition in our body. This can present in patients from adolescent years through adulthood, ranging from fleeting pain to amputations from severe bone infections. We have found that for younger patients, diet plays a lesser part than genetic predisposition and hypoxia.

So how is this treated? We are still researching the best course of action. We can treat with drugs that work by inhibiting the previously specified enzyme: xanthine oxidase. These include oral allopurinol, febuxostat, and even IV pegloticase infusions. But we are primarily focused on prevention and holistic care here, so we would prefer to use supplemental oxygen therapy for those that struggle to maintain oxygen saturations in the healthy ranges. Acetazolamide is also helpful in cases. This medication works to increase our respiratory drive, helping us breathe off CO2 and breathe in more oxygen. Contact us to see what method might be right for you.

This research was brought to us by a stroke of luck. A stranger on an airplane, and a son’s coworker. This stranger happened to be a nephrologist (kidney doctor) who is studying how altitude affects the kidneys. In working with him and his team at University of Colorado Anschutz, the team at Ebert Family Clinic in Frisco, Colorado (9000′) have been ordering broader lab panels (including uric acid) for their patients and seeking those with questionable renal labs. Another patient seen by the Ebert Family Clinic team has been severely impacted by gout. With multiple amputations before the patient’s 30th birthday, this case has motivated the health care team to prevent this from happening to others in their high altitude community.

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Carter Odean is a third-year medical student at Rocky Vista University. He was born and raised outside of Denver, Colorado before heading to Gonzaga University in Spokane, Washington where he studied biology and completed research on an invasive bee species there while playing club lacrosse. After graduating in 2019, he then came back to Denver to complete his Master’s in Biomedical Sciences at Regis University. After Regis, he started as a Clinical Research Coordinator at Anschutz Medical campus, working on multiple Diabetes Mellitus Type 2 research trials. He is in the Rural & Wilderness Track which is his favorite part about school. He plans to work as a rural Pediatrician or Family Medicine Physician. In his free time, you can find him dirt biking, fly fishing, skiing, and relaxing with friends and family. 

References

  1. Schoene, R.B. “High altitude renal syndrome: polycythemia, hyperuricemia, microalbuminuria, and hypertension.” High Alt Med Biol. 2002 Spring;3(1):65-73. doi: 10.1089/152702902753639371. PMID: 11949751.
  2. Bigham, A.W., Lee, F.S. “Tibetan and Andean patterns of adaptation to high-altitude hypoxia.” Hum Biol. 2014 Oct;86(4):321-37. doi: 10.3378/027.086.0401. PMID: 25700353; PMCID: PMC4438718.
  3. Beall, C.M., Cavalleri, G.L., Deng, L., et al. “Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders.” Proc Natl Acad Sci U S A. 2010 Mar 9;107(25):11459-64. doi: 10.1073/pnas.1002443107. Epub 2010 Feb 22. PMID: 20176925; PMCID: PMC2895106.
  4. Simonson, T.S., Yang, Y., Huff, C.D., et al. “Genetic evidence for high-altitude adaptation in Tibet.” Science. 2010 Sep 10;329(5987):72-5. doi: 10.1126/science.1189406. PMID: 20616233; PMCID: PMC3490534.
  5. Schoene, R.B., Swenson, E.R. “Cobalt-Induced Chronic Mountain Sickness: Pathophysiological Mechanisms and Genetic Susceptibility.” High Alt Med Biol. 2017 Mar;18(1):1-5. doi: 10.1089/ham.2016.0106. PMID: 28145824.Baillie, J.K., Bates, M.G., Thompson, A.A., et al. “Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.” Chest. 2007 Dec;132(6):S275. doi: 10.1378/chest.132.6.275. PMID: 18079246.
  6. Yu, K.H., Wu, Y.J., Tseng, W.C., et al. “Risk of end-stage renal disease associated with gout: a nationwide population study.” Arthritis Res Ther. 2012 Jun 27;14(3):R83. doi: 10.1186/ar3818. PMID: 22738152; PMCID: PMC3446515.
  7. Bhat, A., Deshmukh, A., Anand, S., et al. “Acute Myocardial Infarction due to Coronary Artery Embolism in a Patient with Severe Hyperuricemia.” J Assoc Physicians India. 2019 Nov;67(11):90-91. PMID: 31801335.
  8. Khanna, D., Khanna, P.P., Fitzgerald, J.D., et al. “2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia.” Arthritis Care Res (Hoboken). 2012 Oct;64(10):1431-46. doi: 10.1002/acr.21772. PMID: 23024028.
  9. Schoene, R.B., Swenson, E.R. “Treatment of Cobalt-Induced Chronic Mountain Sickness.” High Alt Med Biol. 2017 Mar;18(1):74-77. doi: 10.1089/ham.2016.0135. PMID: 28145823.
  10. Schoene, R.B., Hackett, P.H., Henderson, W.R., et al. “High Altitude Medicine and Physiology, Fourth Edition.” CRC Press, 2007.
  11. Burtscher, M., Mairer, K., Wille, M., et al. “Risk of acute mountain sickness in tourists ascending to 4360 meters by cable car.” High Alt Med Biol. 2004 Summer;5(2):141-6. doi: 10.1089/1527029041352154. PMID: 15265307.
  12. Baumgartner, R.W., Bärtsch, P. “Chronic mountain sickness and the heart.” Prog Cardiovasc Dis. 2010 May-Jun;52(6):540-9. doi: 10.1016/j.pcad.2010.02.009. PMID: 20417390.
Acclimation, Altitude Science, Child Growth & Development, Doc Talk, Genetics, Health, High Altitude

The Frisco Score: A New Tool for Diagnosing HAPE

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by Madison Palmiero, PA-S

While HAPE may be a run-of-the-mill diagnosis for providers with years of experience practicing at altitude, it can be less straightforward for those who are unfamiliar with the condition. There are currently three recognized categories of HAPE. Classic HAPE (C-HAPE)  occurs when someone who resides at low altitude travels to high altitude and develops pulmonary edema. Re-entry HAPE (R-HAPE) occurs when high altitude residents travel to low altitude, then return to high altitude. High-altitude resident pulmonary edema (HARPE) occurs in high altitude residents without a change in altitude. HARPE is often brought on by an upper respiratory tract infection. 

HAPE and pneumonia can have similar presentations including shortness of breath, cough, fatigue, and malaise. Patients with either condition may have decreased oxygen saturation levels and abnormal findings on chest radiography. In response to this phenomena, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, Colorado (9000′) and Sean Finnegan, PA-C set out to develop a scoring system to differentiate the two diagnoses. If providers could easily differentiate between pneumonia and HAPE, this would shorten the time from presentation to diagnosis and would avoid unnecessary antibiotic use.

Dr. Chris and Sean Finnegan, PA-C summarized their research findings into a scoring system named the “Frisco Score”. They analyzed data from St. Anthony Summit Medical Center and associated clinics at or above ~2,760 meters above sea level from January 1, 2018 to May 30, 2023. The study looked at patients under the age of 19 who presented with hypoxemia or other respiratory concerns and had a chest x-ray performed and oxygen saturation measured. The final case review consisted of 138 total patients with 77 diagnosed with HAPE, 38 diagnosed with pneumonia, and 23 diagnosed with concomitant HAPE and pneumonia. Variables found to have no significance included gender, age, heart rate, and temperature. Variables with significance included respiratory rate, number of days ill, oxygen saturation, and chest x-ray findings. These significant variables were used to develop the Frisco Score. They do include a disclaimer that these findings are preliminary results on a small data set. Thus, as of yet, the Frisco Score should not be used on its own to make a diagnosis, but rather should be used as a clinical tool in differentiating conditions with similar presentations. 

Oxygen saturation varied greatly between patients with HAPE and those with pneumonia. Patients diagnosed with HAPE had an average oxygen saturation of 74% and those with pneumonia had an average of 92%. 

Patients who were diagnosed with HAPE had a higher average respiratory rate compared to those diagnosed with pneumonia.

 In patients diagnosed with HAPE, the duration of illness, or number of days ill, was shorter than those diagnosed with pneumonia. 

In comparison of chest x-rays, patients with HAPE were more likely to have diffuse findings and patients with pneumonia were more likely to have focal findings. 

Overall, there were no variables associated with a concomitant diagnosis of pneumonia and HAPE.

The asphalt road in the foreground leads past a sign for Common Spirit St. Anthony Summit Hospital just before the shelter over the entrance to a building labeled "ambulance" with deep green conifer forests stretching halfway up tall grey rocky mountains in the backgroundl.

In summary, patients diagnosed with HAPE had decreased oxygen saturation, increased respiratory rate, and diffuse findings on chest x-ray; while patients diagnosed with pneumonia had a longer duration of illness and focal findings on chest x-ray. The Frisco Score takes these variables into account to help differentiate a diagnosis of HAPE in children. Dr. Chris and Sean Finnegan, PA-C are currently presenting their findings at the 8th World Congress on Mountain and Wilderness Medicine in Snowbird, Utah. They hope that in the near future, the Frisco Score will be used to facilitate the diagnosis of HAPE by providers in high altitude communities state-wide.

References

1. Ebert-Santos, C. (2017). High-Altitude Pulmonary Edema in Mountain Community Residents. High Altitude Medicine & Biology, 18 (3), 278-284. https://doi.org/10.1089/ham.2016.0100

2. Ebert-Santos, C., Finnegan, S. (2024). Differentiating Pneumonia & HAPE in Children.

Acclimation, Altitude Science, Asthma, Child Growth & Development, COVID-19, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering, Pandemic, Sleep at Altitude, Technology

Can I Ever Go Back Up To High Altitude Again? – Recurrence Risk of HAPE & HARPE

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by Taylor Kligerman, PA-S

Can I ever return to high altitude? Do I need to move down to a lower elevation?

Disease processes often differ at high altitudes. Some conditions have only been known to occur at high elevations. Most of the resources cited in this blog refer to ‘high altitude’ being at or above 2,500 meters or 8,200 feet.

Ebert Family Clinic in Frisco, Colorado is at 9,075 ft. Many areas in the immediate vicinity are over 10,000′, with some patients living above 11,000′. Two of the more common conditions seen in patients at Ebert Family Clinic are high altitude pulmonary edema (HAPE) and high altitude resident pulmonary edema (HARPE), similar conditions that affect slightly different populations in this region of the Colorado Rocky Mountains.

In “classic” HAPE, a visitor may come from a low-altitude area to Frisco on a trip to ski with friends. On the first or second day, the person notices a nagging cough. They might wonder if they caught a virus on the plane ride to Denver. The cough is usually followed by shortness of breath that begins to make daily tasks overwhelmingly difficult. One of the dangerous aspects of HAPE is a gradual onset leading patients to believe their symptoms are caused by something else. A similar phenomenon is seen in re-entry HAPE, where a resident of a high altitude location travels to low altitude for a trip and upon return experiences these same symptoms [1].

In HARPE, a person living and working here in Frisco may be getting ill or slowly recovering from a viral illness and notices a worsening cough and fatigue. These cases are even more insidious, going unrecognized, and so treatment is sought very late. Dr. Christine Ebert-Santos and her team at Ebert Family Clinic hypothesize that while residents have adequately acclimated to the high-altitude environment, the additional lowering of blood oxygen due to a respiratory illness with inflammation may be the inciting event in these cases.

In both cases, symptoms are difficult to confidently identify as a serious illness versus an upper respiratory infection, or simply difficulty adjusting to altitude. For this reason, Dr. Chris recommends that everyone staying overnight at high altitude obtain a pulse oximeter. Many people became familiar with the use of these instruments during the COVID-19 pandemic. The pulse oximeter measures what percent of your blood is carrying oxygen. At high altitude, a healthy level of oxygenation is typically ≥90%. This is an easy way to both identify potential HAPE/HARPE, as well as reassure patients they are safely coping with the high-altitude environment [2].

HAPE and HARPE are both a direct result of hypobaric hypoxia, a lack of oxygen availability at altitude due to decreased atmospheric pressures. At certain levels of hypoxia, we observe a breakdown in the walls between blood vessels and the structures in lungs responsible for oxygenating blood. The process is still not totally understood, but some causes of this breakdown include an inadequate increase in breathing rates, reduced blood delivered to the lungs, reduced fluid being cleared from the lungs, and excessive constriction of blood vessels throughout the body. These processes cause fluid accumulation throughout the lungs in the areas responsible for gas exchange making it harder to oxygenate the blood [3].

We do know that genetics play a significant role in a person’s risk of developing HAPE/HARPE. Studies have proposed many different genes that may contribute, but research has not, so far, given healthcare providers a clear picture of which patients are most at-risk. Studies have shown that those at higher risk of pulmonary hypertension (high blood pressure in the blood vessels of your lungs), are more likely to develop HAPE [4]. This includes some types of congenital heart defects [5,6]. High blood pressures in the lungs reach a tipping point and appear to be the first event in this process. However, while elevated blood pressures in the lungs are essential for HAPE/HARPE, this by itself, does not cause the condition. The other ingredient necessary for HAPE/HARPE to develop is uneven tightening of the blood vessels in the lungs. When blood vessels are constricted locally, the blood flow is shifted mainly to the more open vessels, and this is where we primarily see fluid leakage. As the blood-oxygen barrier is broken down in these areas, we may also see hemorrhage in the air sacs of the lungs [3].

One observation healthcare providers and scientists have observed is that HAPE/HARPE can be rapidly reversed by either descending from altitude or using supplemental oxygen. Both strategies increase the availability of oxygen in the lungs, reducing the pressure on the lungs’ blood vessels by vasodilation, quickly improving the integrity of the blood-oxygen barrier.

In a preliminary review of over 100 cases of emergency room patients in Frisco diagnosed with hypoxemia (low blood oxygen content) Dr. Chris and her team have begun to see trends that suggest the availability of at-home oxygen markedly reduces the risk of a trip to the hospital. This demonstrates that patients with both at-home pulse oximeters and supplemental oxygen have the capability to notice possible symptoms of HAPE, assess their blood oxygen content, and apply supplemental oxygen if needed. This stops the development of HAPE/HARPE before damage is done in the lungs. In the case of many of our patients, these at-home supplies prevent emergencies and allow patients time to schedule an appointment with their primary care provider to better evaluate symptoms.

Additionally, Dr. Chris and her team have observed that patients with histories of asthma, cancer, pneumonia, and previous HAPE/HARPE are often better educated and alert to these early signs of hypoxia and begin treatment earlier on in the course of HAPE/HARPE, reducing the relative incidence identified by medical facilities. There are many reasons to seek emergent care such as low oxygen with a fever. Patients with other existing diseases causing chronically low oxygen such as chronic lung disease may not be appropriately treated with  supplemental oxygen, although this is a very small portion of the population. Discussions with healthcare providers on the appropriate prevention plan for each patient will help educate and prevent emergency care visits in both residents and visitors.

A young child with short brown hair and glasses with dark, round frames wears a nasal canula for oxygen.

Studies of larger populations have yet to be published. A review of the case reports in smaller populations suggests that the previously estimated recurrence rate of 60-80% is exaggerated. This is a significant finding as healthcare providers have relied on this recurrence rate to make recommendations to their patients who have been diagnosed with HAPE. A review of 21 cases of children in Colorado diagnosed with HAPE reported that 42% experienced at least one recurrence [7]. This study was conducted by voluntary completion of a survey by the patients (or their families) which could lead to significant participation bias affecting the results. Patients more impacted by HAPE are more likely to complete these surveys. Another study looking at three cases of gradual re-ascent following an uncomplicated HAPE diagnosis showed no evidence of recurrence. The paper also suggested there may be some remodeling of the lung anatomy after an episode of HAPE that helps protect a patient from reoccurrence [8]. Similar suggestions of remodeling have been proposed through evidence of altitude being a protective factor in preventing death as demonstrated by fatality reports from COVID-19[9].

Without larger studies and selection of participants to eliminate other variables like preexisting diseases, we are left to speculate on the true rate of reoccurrence based on the limited information we have. Strategies to reduce the risk of HAPE/HARPE such as access to supplemental oxygen, pulse oximeters, and prescription medications [10] are the best way to prevent HAPE/HARPE. Research should also continue to seek evidence of individuals most at risk for developing HAPE/HARPE [11].

A woman with reddish-brown, straight hair just below her shoulders, wears a white coat over a mustard-colored shirt, smiling.

Taylor Kligerman is a third-year medical student at Rocky Vista University with plans to complete a residency in emergency medicine. She was born and raised in Flossmoor, IL, and became interested in medicine following her first medical mission trip to Gonaïves, Haiti in 2010. Taylor has extensive experience in wilderness and remote emergency medicine. Before starting medical school, she was certified as a wilderness EMT and gained experience in remote areas of Canada and Western North Carolina on whitewater expeditions and as a volunteer with local search and rescue. Her personal interests include camping, skiing, and all paddle sports.

References

  1. Ucrós S, Aparicio C, Castro-Rodriguez JA, Ivy D. High altitude pulmonary edema in children: A systematic review. Pediatr Pulmonol. 2023;58(4):1059-1067. doi:10.1002/ppul.26294
  2. Deweber K, Scorza K. Return to activity at altitude after high-altitude illness. Sports Health. 2010;2(4):291-300. doi:10.1177/1941738110373065
  3. Bärtsch P. High altitude pulmonary edema. Med Sci Sports Exerc. 1999;31(1 Suppl):S23-S27. doi:10.1097/00005768-199901001-00004
  4. Eichstaedt C, Benjamin N, Grünig E. Genetics of pulmonary hypertension and high-altitude pulmonary edema. J Appl Physiol. 2020;128:1432
  5. Das BB, Wolfe RR, Chan K, Larsen GL, Reeves JT, Ivy D. High-Altitude Pulmonary Edema in Children with Underlying Cardiopulmonary Disorders and Pulmonary Hypertension Living at Altitude. Arch Pediatr Adolesc Med. 2004;158(12):1170–1176. doi:10.1001/archpedi.158.12.1170
  6. Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018;19(1):91-98. doi:10.1089/ham.2017.0096
  7. Kelly TD, Meier M, Weinman JP, Ivy D, Brinton JT, Liptzin DR. High-Altitude Pulmonary Edema in Colorado Children: A Cross-Sectional Survey and Retrospective Review. High Alt Med Biol. 2022;23(2):119-124. doi:10.1089/ham.2021.0121
  8. Litch JA, Bishop RA. Reascent following resolution of high altitude pulmonary edema (HAPE). High Alt Med Biol. 2001;2(1):53-55. doi:10.1089/152702901750067927
  9. Gerken J, Zapata D, Kuivinen D, Zapata I. Comorbidities, sociodemographic factors, and determinants of health on COVID-19 fatalities in the United States. Front Public Health. 2022;10:993662. Published 2022 Nov 3. doi:10.3389/fpubh.2022.993662
  10. Luks A, Swenson E, Bärtsch P. Acute high-altitude sickness. European Respiratory Review. 2017;26: 160096; DOI: 10.1183/16000617.0096-2016
  11. Dehnert C, Grünig E, Mereles D, von Lennep N, Bärtsch P. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude. European Respiratory Journal 2005;25(3):545-551; DOI: 10.1183/09031936.05.00070404
Accessibility, Acclimation, Altitude Science, Asthma, Child Growth & Development, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine

Hypoxia in the Emergency Department: Preliminary Analysis of Data from the Highest Atitude Population in North America & Children with Hypoxia

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Hypoxia is a common presentation at the emergency department for the St Anthony Summit Medical Center, located at 2800 meters above sea level (msl) in Colorado. Children under 18 are brought in with respiratory symptoms, trauma, congenital heart and lung abnormalities, and high altitude pulmonary edema (HAPE). Many complain of shortness of breath and/or cough and are found to be hypoxic, defined as an oxygen saturation below 89% on room air for this elevation. Patients who live at altitude may perform home pulse oximetry and arrive for treatment and diagnosis of known hypoxia. Extensive and ongoing analysis of the data from children found to be hypoxic in the emergency department raises many questions, including how residents vs nonresidents present, how often  these cases are preceded by febrile illness and what chief complaint is most frequently cited. 

Understanding the presentation of hypoxia in children at altitude can help ensure that healthcare providers are following a comprehensive approach with awareness of the overlapping symptoms of HAPE, pneumonia and asthma. Below is a graphic summary of 36 cases illustrating the clinical, social and geographic factors contributing to hypoxia at altitude in residents and visitors. A further analysis of over 200 children with hypoxia presenting to the emergency room at 9000 feet is underway including x-ray findings.

The graphs below were created by the author, using data extracted directly from a review of patient charts (specifically, those of children presenting to the local hospital in Summit County, Colorado (9000 feet) with hypoxia).

Graphs 1-4 show chief complaints of cough (CC) and shortness of breath (SOB) compared by age and by residence (residence includes altitudes above 2100 msl, the front range (a high altitude region of the Rocky Mountains running north-south between Casper, Wyoming and Pueblo, Colorado) averaging 1500 msl, and out of the state of Colorado) 

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Graphs 5-6 show presence of fever by residence and by age 

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Graphs 7-8 show presence of asthma by residence and by age 

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Graphs 9 and 10 show lowest oxygen by age at admission and lowest O2 organized by days spent in the county (residents are excluded from this data). 

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Erin Snyder is a new graduate physician assistant who graduated this fall after spending her final rotation in Frisco with the Ebert clinic. She is now working in pediatric hematology at Children’s Hospital Colorado. And her free time she enjoys skiing, hiking and spending time with her cat Charlie.

Accessibility, Acclimation, Altitude Science, Child Growth & Development, Diabetes, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering

The Impact of High Altitude on Diabetes Diagnosis: The Relationship between Hemoglobin A1c and Fasting Plasma Glucose

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Type 2 Diabetes (T2D) has emerged as a global concern, with its prevalence steadily increasing. The test of choice to diagnose and monitor T2D is hemoglobin A1c (HbA1c), which tracks average blood sugar levels over the last three months. Normal HbA1c levels are below 5.7%, 5.7% to 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes. Within the prediabetes range, high HbA1c levels increase the risk of developing T2D. Additionally, levels above 6.5% correlate with greater risk for diabetes complications.1 Fasting Plasma Glucose (FPG) is an additional test that indicates an immediate blood sugar level following a period of fasting. Normal FPG levels are below 100 mg/dL (5.5 mmol/L), 100 to 125 mg/dL (5.6 to 6.9 mmol/L) suggests prediabetes, whereas 126 mg/dL (7 mmol/L) or higher generally indicates diabetes.2 Because HbA1c provides an overview of blood sugar levels spanning the past 2-3 months, it offers a more comprehensive insight into blood sugar management and is the preferred diagnostic test for T2D.3 Recent studies are unveiling discrepancies between HbA1c and glucose testing, prompting discussions on specific diagnostic criteria for different populations.

People living at high altitude experience unique physiological adaptations, such as higher hemoglobin levels and specific glucose metabolism patterns. Acknowledging these adaptations, a 2017 study by Bazo-Alvarez et. al sought to evaluate the relationship between HbA1c and FPG among individuals at sea level compared to those at high altitude.

The study analyzed data from 3613 Peruvian adults without diagnosed diabetes from both sea level and high altitude (>3000m). The mean values for hemoglobin, HbA1c, and FPG differed significantly between these populations. The correlation between HbA1c and FPG was quadratic at sea level but linear at high altitude, suggesting different glucose metabolism patterns. Additionally, for an HbA1c value of 48 mmol/mol (6.5%), corresponding mean FPG values were significantly different: 6.6 mmol/l at sea level versus 14.8 mmol/l at high altitude.

Tall, snowy mountain peaks rise in the distance over rows of deep green pine trees growing out of the hills around a bike. path in the foreground.

This significant difference in predictive values suggests potential controversy in utilizing HbA1c as a diagnostic tool for diabetes in high altitude settings. Using HbA1c at altitude potentially underdiagnoses and under treats patients. To ensure a more accurate diagnosis of T2D at high altitude, reevaluating diagnostic criteria, possibly leaning towards FPG or oral glucose tolerance testing (OGTT) might be necessary.

In conclusion, this study emphasizes the need for careful consideration when diagnosing diabetes in high-altitude regions. Future research is warranted, including studies replicating the findings of the cross-sectional study by Bazo-Alvarez and longitudinal studies exposing the long-term effects of the diagnostic discrepancy of HbA1c in high altitude patients. This additional data will ensure accurate diagnosis and appropriate management of diabetic patients at high altitude.

References

  1. Centers for Disease Control and Prevention. A1C Test. Accessed 12/26/23. Available from: https://www.cdc.gov/diabetes/managing/managing-blood-sugar/a1c.html
  2. World Health Organization. Fasting Blood Glucose. Accessed 12/26/23. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2380#:~:text=When%20fasting%20blood%20glucose%20is,separate%20tests%2C%20diabetes%20is%20diagnosed   
  3. Sherwani, S.I., et al. 2016. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark. Insights. 2016 Jul; 11: 95-104. DOI: 10.4137/BMI.S38440.
  4. Bazo-Alvarez, J. C., et al. Glycated haemoglobin (HbA1c) and fasting plasma glucose relationships in sea-level and high-altitude settings. Diabet. Med. 2017 Jun; 34(6): 804-812. DOI: 10.1111/dme.13335.

Ambra Saurini is a second-year physician assistant student at Red Rocks Community College in Arvada, CO. She was born and raised in Denver, but Italian is her first language and she spent summers visiting her grandparents in Italy. She received her undergraduate degree in integrative physiology from the University of Colorado at Boulder. Before PA school, she worked as a research assistant in the Sleep and Development Lab at CU and as a medical assistant at Panorama Orthopedics and Spine Center. In her free time, she enjoys trying new restaurants and coffee shops, hiking, and spending time outside with her two-year old daughter, Chiara.

Acclimation, Altitude Science, Doc Talk, Genetics, Health, High Altitude

RED FLAGS AT ALTITUDE: When Your Doctor Tells You Your Labs AreNormal But the Results in the Patient Portal Are Flagged

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It comes as no surprise that living at altitude can take some adjustment. Travelers visiting just for a quick ski trip recognize  immediately, sometimes even at Denver International Airport when first arriving at Colorado’s Mile High City at 5280 feet, that the air is “thinner” than where they might have journeyed from. That thinner air we all feel is due to our altitude living at 9,075 feet (2) here in Frisco, CO. Our bodies can feel the atmospheric changes even if we do not recognize them ourselves. As a point of reference, on the rather extreme side, the “death zone” that comes to mind when thinking of the behemoth Mount Everest, is any elevation of 26,247 feet and above (3), a  zone we might not be as familiar with is the deterioration zone which begins at a mere 15,000 feet (3). In this zone, the symptoms are variable, but  common manifestations are lethargy, weight loss, poor appetite, and irritability (4). Altitude experts identify 8,000 feet as the elevation where  symptoms such as headaches and pulmonary edema are more likely to manifest. The good and bad effects of altitude are proportional to the elevation and variable between individuals. For all of you ‘fourteener’ fanatics out there, including myself, this comes as a reminder that we are closer than we think to detrimental elevation in our atmosphere. With this  frame of reference fresh in our minds, let us take a closer look at how living in at the elevation of Frisco, Colorado at 9000 feet or the neighboring towns can affect our health. 

Mountain residents who have blood tests done commonly see “red flags” next to some lab values. In particular, the complete blood count, commonly referred to as CBC. To most of us, those red flags are an alarming indicator that something must be terribly awry but au contraire,  there is an explanation why we need not worry. For those of us living at altitude, there is a reduced atmospheric pressure, so although the fraction of oxygen in the air is still 21%, the molecules are further apart. Fewer oxygen molecules enter our lungs and bloodstream  delivering less oxygen to our tissues(5). Remember now, we are not living on top of Mount Everest, so we are not in any danger, because our bodies are doing behind-the-scenes work for us! Our bodies are adapting by increasing the amount of red blood cells, which carry oxygen in our blood, throughout our bodies so that every organ is being supplied with the good stuff! This is exactly why athletes come here to train, to get their bodies to produce more red blood cells so they can perform at their absolute best. After three months of life in the mountains, nearly everyone has elevated red blood cells, hemoglobin, hematocrit, and red cell indices such as the MCV, (mean corpuscular volume), MCHC (mean corpuscular hemoglobin content) and MCH (mean corpuscular hemoglobin). A “normal” hemoglobin in a man who lived for years in the mountains was a signal to his doctor that the patient was anemic and in fact turned out to have colon cancer.

A more immediate response to the low oxygen environment at altitude is an increase in respiratory rate. In an interview with physician experts on altitude Dr. Elizabeth Winfield and Dr. Erik Swenson on May 30, 2023, both think this is the reason there is often a red flag for the carbon dioxide (CO2) as low, usually 17 to 19 with 20 being normal.  Because this affects the acid base balance, the serum chloride ( Cl) may be slightly elevated, 107 to 108 instead of 106. Dr. Winfield also explains to her patients that fasting for labs may cause mild dehydration leading to a slightly higher BUN, blood urea nitrogen, a marker of kidney function.  Another physiological response to altitude is a lower plasma volume, which may cause slight elevation in the serum protein and albumin.

So when you doctor calls you and tells you your labs are normal, ask them to drill down and explain the red flags.  If you find out something new, please put a comment on our blog and share with the world! Few health care providers really understand all the changes in the human body living in hypobaric hypoxic (low pressure, low oxygen) environments.

References 

1. Image. https://ichef.bbci.co.uk/news/624/cpsprodpb/960F/production/_83851483_c0249925-red_blood_cells,_illustration-spl.jpg. 

2. Town of Frisco Colorado. (2023). Maps. https://www.friscogov.com/your-government/maps/. 

3. Lankford, H. V. (2021). The death zone: Lessons from history. Wilderness & Environmental Medicine, 32(1), pp. 114-120. https://doi.org/10.1016/j.wem.2020.09.002. 

4. West, J. C. (2013). Case law update. Legal liability in emergency medicine and risk management considerations. Journal of healthcare risk management: the journal of the American Society for Healthcare Risk Management, 33(1), pp. 53-60. 

5. Cabrales, P., Govender, K. and Williams, A.T. (2020), What determines blood viscosity at the highest city in the world?. J Physiol, 598: 3817-3818. https://doi.org/10.1113/JP280206

6. Image. https://cdn.allsummitcounty.com/images/content/5717_13913_Frisco_Colorado_Main_Street_lg.jpg

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, Child Growth & Development, Genetics, Health, High Altitude

RSV: The Higher the Altitude, the Higher the Risk

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Respiratory syncytial virus, RSV, is a common disease that predominantly affects infants and children throughout the world. Symptoms include mild fever, runny nose, coughing, and wheezing (CDC, 2021 and is the leading cause of bronchiolitis and pneumonia in children under the age of 1 in the United States. Because of this high risk of lower respiratory symptoms RSV is also the leading cause of hospitalizations within this age group (Sanofi Pasteur, 2021). Testing for RSV is quick and easy. Children under the age of 5 can be tested for RSV with a nasal swab and rRT-PCR test, similar to COVID-19 home tests (CDC, 2021) available at clinics and emergency rooms. . Unfortunately, preventing the spread of RSV and keeping these hospitalization rates to a minimum is more difficult at higher elevations.

One of our patients during admission after being diagnosed with RSV earlier in the day.

Higher elevations affect the body in many ways. The human body physiologically adapts within seconds of exposure to higher altitudes. Respiratory rate increases in order to compensate for the lower amount of oxygen circulating within the body (Scott, 2018). Within days to weeks, the body begins to acclimate to the higher altitude and this hypoxic state by maintaining this increased ventilation rate and increasing the amount of hemoglobin in the body (Scott, 2018). Due to the combination of effects on ventilation and oxygenation, managing respiratory infections like RSV becomes more difficult.

  The correlation between rates of RSV and higher altitudes has been studied more in recent years. It is hypothesized that the physiological changes that the body undergoes at higher altitude predisposes children to respiratory illnesses including RSV (Shi et al., 2015). In one study done in Colorado, the incidence of RSV within the population was higher than those at moderate and lower elevation areas. The rates of hospitalization increased 25% with children under the age of 1 and up to 53% with children between 1 and 4 (Choudhuri et al, 2006). Data shows that as altitude increases, the incidence of RSV increases, with elevations over 2500m considered as a modest predictor of RSV-related hospitalizations. The incidence of morbidity associated with RSV increases with higher elevation as well (Wu et al., 2015). This increased morbidity is attributed to the thick secretions that is caused by the virus. Since infants breathe through their nose until age 3, this collection of mucus causes respiratory issues including pauses in breathing with cyanosis called apnea. With studies showing the increased incidence, hospitalizations, and morbidity of RSV at higher altitudes, diagnoses of RSV should not be downplayed in children living at high altitudes.

Photo of the same patient as above on home oxygen after being discharged from the hospital.

It is important for providers and parents to be aware of the higher risk for more severe disease progression faced by children who reside at higher altitudes. Parents should recognize the symptoms of RSV and practice proper handwashing techniques to prevent the further spread of this disease within the community. Health care providers within these high-altitude areas should consider additional interventions and treatments such as home oxygen or nasal suctioning which may be beneficial to preventing hospitalizations due to RSV. Dr. Chris advises parents with older children in daycare or preschool to consider keeping them home during RSV season (November-April) when they have a new baby in the house. Although it is imperative to properly diagnose and treat RSV to avoid hospitalizations, obtaining a chest x-ray and treating with medications like albuterol or steroids is unnecessary. Ultimately, although RSV is a benign disease to most, in areas of higher elevation, it must be taken seriously order to prevent unfavorable outcomes.

References

Centers for Disease Control and Prevention. (2021, September 24). Symptoms and care of RSV (respiratory syncytial virus). Centers for Disease Control and Prevention. Retrieved April 28, 2022, from https://www.cdc.gov/rsv/about/symptoms.html 

Choudhuri, J. A., Ogden, L. G., Ruttenber, A. J., Thomas, D. S., Todd, J. K., & Simoes, E. A. (2006). Effect of altitude on hospitalizations for respiratory syncytial virus infection. Pediatrics, 117(2), 349–356. https://doi.org/10.1542/peds.2004-2795

Sanofi Pasteur. (2021). Rethink RSV. Retrieved April 28, 2022, from https://www.rethinkrsv.com/

Scott, B. (2018, June 13). How does altitude affect the body? Murdoch University. Retrieved April 28, 2022, from https://www.murdoch.edu.au/news/articles/opinion-how-does-altitude-affect-the-body#:~:text=Many%20people%20who%20ascend%20to,lethargy%2C%20dizziness%20and%20disturbed%20sleep 

 Shi, T., Balsells, E., Wastnedge, E., Singleton, R., Rasmussen, Z. A., Zar, H. J., Rath, B. A., Madhi, S. A., Campbell, S., Vaccari, L. C., Bulkow, L. R., Thomas, E. D., Barnett, W., Hoppe, C., Campbell, H., & Nair, H. (2015). Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis. Journal of iglobal health, 5(2), 020416. https://doi.org/10.7189/jogh.05.020416

Wu, A., Budge, P. J., Williams, J., Griffin, M. R., Edwards, K. M., Johnson, M., Zhu, Y., Hartinger, S., Verastegui, H., Gil, A. I., Lanata, C. F., & Grijalva, C. G. (2015). Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru. PloS one, 10(6), e0130233. https://doi.org/10.1371/journal.pone.0130233

Claire Marasigan is a 2nd year PA student currently studying at Midwestern University in Glendale, Arizona. Claire has lived her entire life in Arizona and went to Grand Canyon University for her undergraduate degree in Biology. Prior to PA school, she was a medical scribe trainer at St. Joseph’s Hospital in Phoenix. In her free time, she loves to cook, try new restaurants with friends, and play with her dog, Koji. 

Acclimation, Alcohol at Altitude, Altitude Science, Athletic Training, Genetics, Health, High Altitude, High Altitude Training & Fitness, Sickle Cell

Dad, put your clothes on! Unique presentations of altitude illness, a Discussion with EMS director Thomas Resignolo

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After his father-in-law arrived in the mountains, Thomas noticed later that night he seemed intoxicated despite not seeing him drink alcohol. Thomas woke up the next morning to see him reading the paper in nothing but black socks and a black tie. Thomas knew right away he wasn’t drunk, he had high altitude cerebral edema (HACE). HACE is a complication of acute mountain sickness (AMS). HACE can occur from increased pressure in the blood vessels in the brain, leading to fluid leakage and swelling (edema). This increased vessel pressure can result from the lower atmospheric pressure at high altitude1. Breathing in lower atmospheric pressure gives you less oxygen molecules per breath. Thomas estimates that EMS in Summit County see one case of HACE a year. EMS look for two hallmark signs of HACE, altered mentation and ataxia. When EMS arrive to a patient with altered mentation, they have the patient walk heel-to-toe to evaluate for ataxia. If ataxia is present, immediate descent is necessary. Rapid descent is necessary because HACE can progress rapidly. Years ago, Thomas had a patient walk into the emergency department and die within 10 minutes after arrival. Unlike high altitude pulmonary edema (HAPE), descent is the only cure for HACE.

HAPE is a more common complication of AMS. Similar to HACE, edema occurs from the high pressure inside pulmonary blood vessels pushing fluid into the lungs. The high pressure is caused by a rapid vasoconstriction response to hypoxia or low oxygen partial pressures. Luckily, HAPE has a simple treatment, oxygen. Therefore, visitors with HAPE do not need to descend to lower altitude as with HACE. HAPE is much harder to recognize than HACE and EMS is well trained in how to recognize it. Often, headache is the only symptom2. Thomas explains the HAPE protocol for EMS: In the first 20 seconds of arriving, an oxygen saturation is obtained; they obtain vitals in the next two minutes and then start high flow oxygen if the saturation is below 89%; they then listen to the lungs for signs of fluid. EMS does not treat HACE or HAPE with any medications since descent and oxygen are the effective treatments.

So, who is prone to AMS?

Unfortunately, better physical fitness does not protect you from AMS. Thomas reports that athletes with resting heart rates of 40 or below have a difficult time acclimating. Younger age also doesn’t mean easier acclimation. According to Thomas, the best age for acclimation is late 30s/early 40s. Surprisingly, previous hypoxia can help acclimation to high altitude. For example, Thomas reports that smokers have an easier time acclimating because their body is used to having the vasoconstriction response to hypoxia and breathing faster and deeper to get adequate oxygen intake.

But don’t worry, your conditioning wasn’t for nothing. A healthy diet and regular exercise prevents heart disease. Thomas estimates there are about 12 acute MI’s on the ski hill each year. These patients usually have to be transported to Denver for a stent to be placed. Exacerbation of coronary artery disease (CAD) is so common that EMS refers to altitude travel as the “altitude stress test.” This mimics a cardiac stress test in those with CAD, producing chest pain that wasn’t present at lower altitude.

Those with sickle cell disease are at risk of developing sickle cell crisis when traveling to high altitude. The lower atmospheric pressure allows the normal red blood cells to lose their integrity and become sickle. Thomas reports that EMS encounters this every couple months in patients (usually of Mediterranean descent) that present with diffuse abdominal pain with no obvious cause. This pain results from the sickle cells aggregating together and causing an occlusion. The occlusion leads to tissue hypoxia and ischemia3. These patients are transported to the hospital for treatment.

How can mountain tourists avoid AMS?

Thomas’s first recommendation is to take a staggered stop for one night at an elevation of 5,000-6,000ft, like Denver. When arriving to altitude, take it easy the first 3 days: don’t drink alcohol and do light activity. Save the long hike for the end of the trip. Also avoid substances that blunt the respiratory system like alcohol, opioids, benzodiazepines, etc. Prepare by hydrating the week before and keep drinking plenty of water while on the trip. If you have had a previous episode of AMS, you can speak to your medical provider about prophylactic medication to take before arriving at high altitude.

References

1. Hackett PH, Dietz TE. Travel Medicine. Fourth ed. Edinburgh: Elsevier; 2019. https://www-clinicalkey-com.ezproxy2.library.drexel.edu/#!/content/book/3-s2.0-B9780323546966000422?scrollTo=%23hl0000521. Accessed November 22, 2021.

2. Schafermeyer, R. W. DynaMed. Acute Altitude Illnesses. EBSCO Information Services. https://www.dynamed.com/condition/acute-altitude-illnesses. Accessed November 19, 2021.

3. Sheehan VA, Gordeuk VR, Kutlar A. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. In: Kaushansky K, Prchal JT, Burns LJ, Lichtman MA, Levi M, Linch DC. eds. Williams Hematology, 10e. McGraw Hill; 2021. Accessed November 23, 2021. https://accessmedicine-mhmedical-com.ezproxy2.library.drexel.edu/content.aspx?bookid=2962&sectionid=252529206

Samantha Fredrickson is currently a student in Drexel University’s Physician Assistant program.