In one breath
Height lowers the partial pressure of inspired O₂, so less O₂ reaches the tissues. The first answer is hyperventilation, which begins the moment alveolar PO₂ drops below about 60 mmHg — around 4500 m (14000 feet) — and then grows over hours to weeks as the CSF and the kidney let go of the alkalosis that was holding it back. Over days, extra red cells, more 2,3-DPG, a faster heart and a remodelled muscle bed all push more O₂ into the tissues. This whole adaptation, called acclimatization, works up to about 18000 feet; above that a climber needs O₂ to survive.
Builds on: Chemical control of breathing · Oxygen–hemoglobin dissociation curve · Leads to: High altitude illness · Hypoxia
Compensatory mechanisms
- A fall in PIO₂ at altitude means less O₂ delivered to the tissues, so a set of compensatory mechanisms switches on to keep delivery near normal.
- The immediate and most important of these is hyperventilation.
- Hypoxia does not drive ventilation appreciably until alveolar PO₂ falls below 60 mmHg.
- Alveolar PO₂ normally reaches that 60 mmHg mark at an altitude of about 4500 m (14000 feet).
| Landmark | Value |
|---|---|
| Alveolar PO₂ that starts hypoxic drive | 60 mmHg |
| Altitude giving that PO₂ | 4500 m (14000 ft) |
| Ceiling of adaptation | 18000 ft |
Two heights, two meanings
14000 ft is where hypoxic hyperventilation becomes significant; 18000 ft is the highest level a person can adapt to at all. Students swap them constantly. Above 18000 ft, O₂ inhalation is needed for survival, however long you stay.
Stages of compensation
Hypoxic hyperventilation comes in two stages.
First stage: instant but small
- Begins immediately on exposure to hypoxia.
- Driven by hypoxic stimulation of the carotid bodies (peripheral chemoreceptors).
- The rise in ventilation is small compared with the second stage, because the hyperventilation itself blows off CO₂:
- arterial PCO₂ falls, and
- arterial pH rises (alkalosis).
- Low PCO₂ and alkalosis together blunt the hypoxic response, so the two forces work against each other.
Second stage: slow and sustained
- Ventilation climbs slowly over 8 to 10 hours, then stays up.
- The sustained rise is ventilatory acclimatization: the response of prolonged, not acute, hypoxia.
- Hyperventilation reaches a stable plateau after about 2 weeks.
Two mechanisms produce it:
- Chemoreceptor mechanism
- CSF pH is more alkaline in the acute phase.
- The hypoxia-driven ventilation brings it near normal by moving HCO₃⁻ out of the CSF.
- With prolonged hypoxia, the carotid body’s sensitivity to arterial PO₂ itself changes.
- Renal mechanism
- Alkaline blood pH is what opposes the hypoxic response.
- The kidney compensates by excreting more HCO₃⁻.
- Blood pH returns toward normal in about 3 days, so the alkaline brake is released.
Both do the same job: they remove the alkalosis that was opposing the hypoxic drive. Once it is gone, hypoxia is free to raise minute ventilation further, and ventilation settles at a new steady state.
Draw it: two-stage ventilation curve
Plot time on the x-axis (minutes → hours → days → 2 weeks, not to scale) and minute ventilation on the y-axis. Draw a small vertical step the instant hypoxia starts, label it “stage 1 — carotid body, blunted by low PCO₂ and alkalosis”. Then a slow rise over 8–10 hours flattening into a plateau by 2 weeks, labelled “stage 2 — ventilatory acclimatization”. Mark the pre-exposure level as a dashed baseline and show that the curve never returns to it.
Acclimatization: what it means
- Live at altitude long enough and the body slowly adapts to the new environment. That adaptation is acclimatization.
- It starts within 12 hours and takes several days to weeks to complete.
- The maximum height to which adaptation occurs is 18000 feet. Above that, survival needs O₂ inhalation.
- The changes fall on the respiratory and cardiovascular systems, the blood and the tissues. They all exist for one purpose: to get more O₂ into the cells.
Respiratory changes
The peripheral chemoreceptors are what hypoxia acts on first, and from there:
- Pulmonary ventilation rises, by both rate and depth of breathing.
- CO₂ is washed out, so respiratory alkalosis develops — and alkalosis counteracts the stimulating effect of hypoxia.
- Bicarbonate is then dumped into the urine, which drags blood pH back down and leaves the urine alkaline. That is what lets the respiratory centre go on answering hypoxia, and keeps ventilation high.
- Ventilation also rises steadily because of active transport of H⁺ into the CSF.
- The response eases off slowly after four days, but stays permanently above the pre-exposure level.
Ventilatory equivalent (VE) is the better index of the ventilatory response:
- Ventilatory equivalent = expired minute volume ÷ O₂ consumption.
- It increases as altitude increases — the higher you go, the bigger the response.
- Watch the notation: the book writes VE both for the index and for expired minute volume (with VO₂ for O₂ consumption). Define your symbols when you write it out.
The book reads both ways after day 4
One line says the ventilatory response decreases slowly after four days while staying above baseline; the next paragraph says that after about four days it slowly increases, in proportion to the altitude. Safe answer for a written paper: after about four days the response settles, remains permanently above the pre-exposure level, and is larger the higher the altitude.
Applied: people born at altitude
Diffusion capacity for O₂ and maximum voluntary ventilation (MVV) are both greater in permanent high altitude residents than in newcomers — a structural, lifelong adaptation rather than a few weeks of acclimatization. See Lung volumes, capacities and spirometry for how MVV is measured.
Draw it: altitude versus ventilatory equivalent
One simple graph: altitude (feet or metres) on the x-axis, ventilatory equivalent VE on the y-axis. Draw a single line rising steadily from left to right. Label the y-axis in full — “VE = expired minute volume ÷ O₂ consumption” — and write the one-line conclusion under it: VE rises with altitude.
Hematological changes
These work in two ways: more red cells, and better unloading from the cells you have.
- Erythropoietin (Ep): hypoxia stimulates Ep production. Ep-driven erythropoiesis begins in about 3 days and continues for as long as the person stays high. The larger red cell mass carries more O₂ to the tissues.
- 2,3-DPG: its concentration in red cells rises, and that tips the oxyhemoglobin dissociation curve rightward, which helps Hb let go of O₂ in the tissues.
The curve moves left first
Early on, the alkalosis of hyperventilation shifts the O₂–Hb curve to the left. Only later, as 2,3-DPG rises, does it swing to the right. A question asking about the acclimatized climber wants the right shift; one asking about the first hours wants the left. See Oxygen–hemoglobin dissociation curve.
Cardiovascular changes
On arrival: three things rise together — heart rate, cardiac output, blood pressure.
- These rises come from hypoxic activation of the sympathoadrenal axis.
- Later: heart rate drifts back to normal, though some people keep a high blood pressure. The raised cardiac output helps blood flow stay high.
- Hypoxia widens the systemic vessels, adding further to blood flow and tissue O₂ supply.
- The price of a bigger red cell mass: marked polycythemia raises hematocrit and blood viscosity, which raises the workload on the heart, and the heart responds with hypertrophy.
Polycythemia cuts both ways
Extra red cells improve oxygenation, but past a point the thicker blood costs more in cardiac work than it gains in O₂ carriage. This is the same viscosity that drives Monge’s disease.
Tissue changes
Mostly in skeletal muscle:
- The number of capillaries increases.
- The number of mitochondria in the cells increases.
- The activity of oxidative enzymes such as cytochrome oxidase increases.
- Myoglobin content increases.
- Angiogenesis: chemicals released by hypoxic tissue stimulate the formation of new blood vessels.
Worth knowing, though not in your pages: read the list as two halves — items 1 and 5 shorten the diffusion distance from blood to cell, while items 2, 3 and 4 raise the cell’s own capacity to store and use the O₂ that arrives.
Other changes
The book sends the remaining changes to its chapter on Environmental Physiology rather than covering them here, so your pages hold nothing further on them.
Worth knowing, though not in your pages: the standard extras usually quoted are loss of appetite with weight loss, a diuresis in the first days of ascent, and impaired sleep with periodic breathing at night.
Exam-answer skeleton: "Describe the physiological changes following ascent to high altitude (acclimatization)" (long essay)
- Why: PIO₂ falls with altitude, so tissue O₂ delivery falls; hypoxic drive needs alveolar PO₂ below 60 mmHg, reached at 4500 m (14000 ft).
- Define acclimatization; it starts within 12 hours, takes days to weeks, and works up to 18000 ft.
- Hyperventilation in two stages: carotid body (immediate, blunted by low PCO₂ and alkalosis), then ventilatory acclimatization over 8–10 hours to a plateau at 2 weeks.
- Its two mechanisms: chemoreceptor (HCO₃⁻ out of CSF, altered carotid body sensitivity) and renal (HCO₃⁻ excreted, alkaline urine, pH normal in ~3 days).
- Respiratory changes; ventilatory equivalent rises with altitude; higher diffusion capacity and MVV in permanent residents.
- Hematological changes: erythropoietin from day 3, raised red cell mass; 2,3-DPG and the right shift (left shift initially).
- Cardiovascular changes: early rise in heart rate, cardiac output and blood pressure; systemic vasodilation; polycythemia → viscosity → cardiac hypertrophy.
- Tissue changes in skeletal muscle: capillaries, mitochondria, oxidative enzymes, myoglobin, angiogenesis. Close by naming the failures of adaptation (High altitude illness).
Asked in exams
- Breathing at high altitude, and acclimatization: Oct 2024, 5 marks