Last October, my daughter Elizabeth and I stood at Londorossi gate (elevation 2,250 metres), the western entrance to Mount Kilimanjaro National Park in Tanzania, ready to begin the nine-day Lemosho route up Mount Kilimanjaro. Climbing “Kili” would fulfil a dream I’ve had since working as a medical student in Kenya. Elizabeth’s dream was to ensure her dad came back in one piece. Unlike Mount Everest, Kilimanjaro is a hike, not a technical climb requiring ropes or crampons. However, as a cardiologist and researcher in oxygen sensing, I knew that our key challenge would be the lack of oxygen — a condition called hypoxia. Altitude and oxygenHypoxia occurs at altitude. At sea level, gravity creates barometric pressure, which compresses nitrogen and oxygen, accounting for Earth’s oxygen-rich atmosphere. However, gravity diminishes with distance from the planet’s centre. At altitude, the low barometric pressure causes gases to expand, meaning there are fewer molecules of oxygen per volume of air. Mount Kilimanjaro, one of the world’s seven summits, is Africa’s highest point at 5,895 metres and the world’s tallest free-standing mountain. At its summit, barometric pressure falls 50 per cent compared to sea level (around 50 kiloPascals compared to 101 kiloPascals), so although oxygen still makes up 21 per cent of air, there are only half as many oxygen molecules in each breath. Venture above 2,400 metres and you may develop acute mountain sickness (AMS) as a result of hypoxia. At altitudes of around 4,000 to 6,000 metres, the chances of developing AMS are 50/50.Fortunately the risk of the more life-threatening hypoxia-related conditions — like high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE) — is lower. Acute mountain sickness is defined by a constellation of symptoms, including headache, nausea and vomiting, loss of appetite and dizziness. HAPE and HACE are different than acute mountain sickness. HAPE is driven by excessive hypoxic constriction of the lung’s arteries (called pulmonary arteries). The pressure in these arteries rises, flooding the lung’s airways with bloody fluid, causing severe shortness of breath, bloody sputum and low blood oxygen. Even more severe is HACE (hypoxic brain swelling), which shows up as severe headache, disorientation and imbalance. While one may endure acute mountain sickness with minor medical assistance, both HAPE and HACE require immediate medical intervention and rapid descent. However, distinguishing acute mountain sickness from early HAPE or HACE and choosing to descend is not always easy, particularly as climbers are often motivated to summit. Careful monitoring by impartial, safety-focused guides with twice daily oximetry is important. Oximetry measures oxygen in blood using a probe placed on the finger.By the time we reached Barafu base camp (4,673 metres), our oxygen saturations had dropped from over 95 per cent at sea level to 87 per cent and 83 per cent. Those with oxygen saturations below 80 per cent at base camp are advised not to proceed to the summit. Once the decision to descend due to low oxygen saturation is made, the choices are to walk down (if able), to be wheeled down on a stretcher or to take a helicopter, which is expensive and not without its own risks.Aspiring climbers should be aware of three factors relating to hypoxia that can reduce their risk of altitude sicknesses and make climbing safer:1. How the body detects hypoxiaYour body has oxygen sensors to detect hypoxia. These sensors are mitochondria, tiny intracellular powerhouses that trigger adaptive responses to boost oxygen uptake and delivery to vital organs. In the carotid body — a tiny sensor in the carotid artery — and in the lung’s pulmonary arteries, mitochondria produce signalling molecules (called oxygen radicals) that trigger responses. These responses include neurotransmitter release, contraction of lung blood vessels and changes in gene expression. The carotid body samples blood headed to the brain and, if it is acidic or hypoxic, signals the brain to increase the depth and rate of breathing. This is a helpful response because it increases ventilation, bringing more oxygen into your body.A similar sensor in the lung’s pulmonary arteries constricts those arteries in response to hypoxic air (hypoxic pulmonary vasoconstriction, or HPV). HPV is helpful when lung hypoxia involves only a segment of lung, as in pneumonia. But at altitude, where the entire lung is filled with hypoxic air, HPV raises the pressure in the pulmonary arteries, which promotes fluid leakage from blood vessels into the airways, causing HAPE.2. Acclimatization is key to surviving hypoxiaSlow ascent gives oxygen sensors time to condition climbers to function in the rarified air at altitudes like Kilimanjaro. The first adaptation, carotid body activation, happens quickly: breathing increases within minutes of hypoxic exposure. Hours later, gene and protein expression changes. This is due to activation of transcription factors that control genes’ on and off switches. One such transcription factor that is activated by hypoxia, named HIF-1, regulates the hormone erythropoietin. More erythropoietin means more production of hemoglobin and red blood cells which increases the blood’s oxygen-carrying capacity. Third, with a slow climb and sustained hypoxia, HPV gradually lessens, preventing pulmonary hypertension and HAPE. Our guides were very familiar with the necessity of acclimatization, and cheered us on with the refrain “Pole pole,” Swahili for “slowly slowly.” Going slowly reduces the risk of developing acute mountain sickness. Like the parable of the tortoise and the hare, it more often strikes fit young people, whose bravado and strength allow rapid ascent, rather than slow-moving seniors. In addition to going “pole pole,” one can improve the chances of summiting by choosing a longer route (on Kilimanjaro, ideally a six- or seven-day ascent, like the Lemosho route) and following a “climb high, sleep low” philosophy: Hike to a higher altitude each day and then descend to your campsite. Dr. Peter Hackett, an experienced mountaineer, documented the importance of acclimatization in a 1976 study. Of 278 unacclimatized hikers ascending to 4,243 metres en route to Everest base camp, he found that 53 per cent developed acute mountain sickness; fewer experienced HAPE (2.5 per cent) or HACE (1.8 per cent). Acute mountain sickness was commonest among younger climbers and those who began their hike at 2,800 metres (after flying in), rather than those who hiked to the starting point at that altitude. Among those who did not acclimatize, acute mountain sickness incidence was reduced by taking acetazolamide, a drug that enhances breathing and suppresses HPV. A more recent study further illustrates the dangers of rapid ascent, finding that 2.5 per cent of hikers trekking to 5,500 metres over four to six days developed HAPE, compared to 15.5 per cent of those airlifted directly to 5,500 metres.3. Medications can helpCertain medicines do prevent and/or treat high altitude illnesses, increasing the chances of a safe climb by enhancing breathing and suppressing HPV (acetazolamide, brand name Diamox), suppressing HPV (sildenafil, brand name Viagra; and calcium channel blockers like nifedipine) and preventing inflammation (ibuprofen, brand name Motrin; and dexamethasone). Our own Kilimanjaro medicine kit included three prescription medications (acetazolamide, sildenafil and dexamethasone) and one over-the-counter medicine (ibuprofen).I’d like to stress that this article is not intended as medical advice. See your physician for fitness confirmation and prescriptions (and try any medicine pre-climb to check for allergies or side-effects) prior to climbing. Most of the medications recommended by the Wilderness Medicine Society’s 2024 Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness require a prescription.Lest you think that using medications is a cheat, trust me: The climb will be challenging despite pharmacological assistance. Elizabeth and I safely summited. Emerging happy but tired through the Mweka gate (1,680 metres), we felt gratitude to our guides, respect for the mountain and pride in realizing our dreams together.This article was co-authored by Elizabeth Archer MFA, of Chicago, Illinois. She is a Canadian-Ukrainian playwright.Stephen L Archer receives funding from CIHR