# High Altitude Physiology > High altitude physiology for MBBS Physiology — hypobaric hypoxia, acclimatisation timeline, HAPE HACE and acetazolamide prophylaxis explained. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/high-altitude-physiology - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "High Altitude Physiology", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/high-altitude-physiology ## Direct answer Barometric pressure at the summit of Everest is about 253 mmHg, so even with 100% saturation of the available air the wet inspired oxygen partial pressure is only about 43 mmHg — the human body survives there only through acclimatisation. The sequence runs: immediate hyperventilation driven by peripheral chemoreceptors (blunted initially by respiratory alkalosis), renal bicarbonate excretion over the next days allowing ventilation to climb further, erythropoietin-driven polycythaemia over weeks, and rising 2,3-DPG, capillary density and oxidative enzymes over months. Failure of adaptation produces acute mountain sickness, high-altitude pulmonary oedema and high-altitude cerebral oedema. ## What you must remember - Acute mountain sickness begins above about 2,500 m: headache, nausea, fatigue, poor sleep — usually 6–12 hours after arrival; it is a predicted consequence of ascent rate, not a sign of weakness. - Immediate acclimatisation: hypoxic ventilatory response through carotid body stimulation; the resulting respiratory alkalosis initially restrains medullary chemoreceptors. - Over 1–3 days, CSF and renal bicarbonate fall (active transport plus bicarbonate diuresis), pH normalises, and ventilation rises further — the single most important acclimatisation step. - Erythropoietin rises within hours; reticulocytes by day 3–5; haemoglobin can reach 18–20 g/dL with chronic exposure — the basis of Monge's chronic mountain sickness (excessive polycythaemia with hypoventilation). - 2,3-DPG increases, shifting the haemoglobin dissociation curve right and aiding tissue unloading. - Hypoxic pulmonary vasoconstriction — the lung's unique response to low alveolar oxygen — raises pulmonary artery pressure and underlies HAPE, which typically strikes on day 2–4 with exertional dyspnoea, cough and pink frothy sputum. - HAPE management: descent, supplemental oxygen, nifedipine; HACE (ataxia, confusion) — dexamethasone and urgent descent. - Prophylaxis: graded ascent (sleep no more than 300–500 m higher per day above 3,000 m) and acetazolamide 125–250 mg twice daily, which produces a metabolic acidosis that sustains hyperventilation, including during the periodic breathing of altitude sleep. - Indian context: soldiers and workers deployed to Ladakh and the Siachen glacier live for months at these pressures; native Tibetan and Himalayan populations show genetic adaptation with better oxygen handling at extreme altitude. ## Acclimatisation read as a timeline Fly from Delhi to Leh at 3,500 m and the clock starts. Within minutes, the carotid bodies sense a falling arterial oxygen tension and hyperventilation doubles — but each breath blows off carbon dioxide, the CSF alkalises, and the medullary chemoreceptors apply the brake; ventilation settles at a partial rise. Over the next 24–72 hours the choroid plexus pumps bicarbonate out of CSF and the kidney excretes it, pH comes back toward normal, and the hypoxic drive is unmasked — ventilation now far above the sea-level value, arterial carbon dioxide in the low 30s or lower. Sleep shows the signature: periodic (Cheyne-Stokes) breathing as the hypoxic drive and the wakeful behavioural drive oscillate, and acetazolamide dampens exactly this cycling. Weeks follow. Erythropoietin has already risen within hours of arrival; new red cells raise oxygen-carrying capacity, and the haematocrit creeps up as plasma volume contracts — a rapid early advantage before the cells themselves accumulate. Months of residence add capillaries, mitochondria, myoglobin and oxidative enzymes in muscle, so diffusion distance shortens and extraction improves. Above roughly 5,500 m, however, deterioration replaces adaptation: weight loss, sleep fragmentation and gradual deconditioning — mountaineers call the zone above 8,000 m the death zone, where no human acclimatises and time is strictly borrowed. ## Where students slip Two questions expose memorised rather than understood answers. Why does acetazolamide prevent mountain sickness — not by adding oxygen but by acidifying: the drug inhibits renal carbonic anhydrase, bicarbonate is lost, the mild metabolic acidosis keeps ventilation driven even during sleep, which is why it is started the day before ascent. Why does the lung constrict when hypoxic — contrary to every systemic vascular bed — because it diverts blood from poorly ventilated alveoli; at altitude, with the whole lung hypoxic, the response instead loads the right ventricle and unevenly over-perfuses some capillaries, which is the mechanical seed of HAPE. Also keep the two oedemas distinct: HAPE is a lung problem of pressure and permeability with a normal brain; HACE is cerebral vasogenic oedema with ataxia as the red-flag sign. ## Frequently asked questions ### Why does hyperventilation at altitude initially fail to reach its full potential? Hypocapnic respiratory alkalosis raises CSF pH and restrains medullary chemoreceptors until bicarbonate is actively transported out over 1–3 days. ### What makes acetazolamide useful in mountain sickness prophylaxis? It causes a bicarbonate diuresis and mild metabolic acidosis that sustains hyperventilation and abolishes altitude periodic breathing during sleep. ### What is the mechanism of high-altitude pulmonary oedema? Uneven hypoxic pulmonary vasoconstriction over-perfuses some capillaries, producing stress failure of their walls and a high-pressure protein-rich leak. ### Why does haemoglobin rise at high altitude and over what time course? Hypoxia-stimulated erythropoietin rises within hours, reticulocytes appear in days, and haemoglobin can approach 20 g/dL over weeks of continuous exposure. ### What distinguishes HACE from acute mountain sickness? HACE adds neurological dysfunction — ataxia and altered consciousness — and demands dexamethasone with immediate descent, whereas simple AMS is headache-predominant.