Adaptation to high altitude

Lecture objectives
1.  List the potential problems faced by man at altitude
2.  State normal sea level barometric pressure, oxygen fraction and partial pressure of
oxygen (PO2) at and explain how they are affected by altitude.
3.  Explain why humidifying the inspired air as it passes through the airways causes a
larger percentage reduction on PO2 at high altitude than at sea level.
4.  Describe the ventilatory response and the effects on arterial PO2 and PCO2 of acute
exposure to altitude. How do these change over the subsequent days.
5.  Describe the other processes that contribute to altitude acclimatisation. Explain how
these responses may differ in acclimatised lowlanders and native highlanders.
6.  Outline the features of the different forms of altitude-related illnesses (acute
mountain sickness. High altitude pulmonary oedema, high altitude cerebral oedema
and chronic mountain sickness)
7.  Describe the effect of altitude on exercise performance. What are the advantages and
disadvantages of training at altitude? Is there any evidence that athletic performance
at sea level can be enhanced using the changes that happen during altitude
acclimatisation?

Fractional concentration of oxygen = 0.209 (20.9%) at all altitudes! Mexico City, 7,350 ft, 2240 m
Quilcha: where the miners lived , 17,500 ft, 5334 m
Pressure in the lungs is close to barometric pressure:! Aucanquilcha: Chile (highest mine, now abandoned),19,000 ft, 5800 m
Everest summit: 29,035 ft,
At sea level average PB = 760 mmHg!
therefore:! M Barometric pressure
Moist inspired PO2
PO2 dry air at sea level = 760 x .209 = 159 mmHg!
Q
As air is inhaled it is diluted with water vapour. saturated water vapour A
pressure at constant 37oC = 47 mmHg.!
E
The total pressure of the other gases is: PB - 47 mmHg!
∴ moist inspired PO2 = 0.209 x (760 - 47) = 149 mmHg!

1 kPa = 7.5 mmHg ! !1 mmHg = 0.133 kPa!

Everest summit = 8, 850 m = 29,035 feet! Barometric pressure on the summit of Everest!
here PB = 250 mmHg approx.!
dry PO2 = 250 x 0.209 = 52.3 mmHg!
and moist PO2 = (250 - 47) x 0.209 = 42.4 mmHg!

note: the affect of moistening the inspired air proportionally greater at

altitude:!
! ! ! ! ! ! !sea level! ! ! ! ! ! !Everest summit!
dry PO2! ! ! 159 mmHg (21.1 kPa) ! 52.3 mmHg (7 kPa)!
saturated at 37oC ! 149 mmHg (19.9 kPa) 42.4 mmHg (5.65 kPa)!
! ! ! ! ! ! !(about 6% fall) ! ! ! !(about 19% fall)!
 Everest
(‘Chomolungma’ = The Mountain So High No Bird Can Fly Over It)
May 8th 1978 Reinhold Messner with Peter Habeler reached the
8th June 1924, George Mallory/Andrew Irvine last seen high on the summit Everest without the use of bottled oxygen.
north east ridge of Everest. The body of Mallory was found on
Everest, May 1st 1999. It is not known whether they ever reached the "In my state of spiritual abstraction, I no longer belong
summit.! to myself and to my eyesight. I am nothing more than a
Why do you want to climb Everest? Mallory: “Because it’s there” single narrow gasping lung, floating over the mists and
summits."
1952 A Swiss team including Raymond Lambert (Swiss) and Tenzing
Norgay made two unsuccessful attempts. Problems with design of In 1980 Messner completed a solo ascent without oxygen.
their oxygen equipment and inadequate water. They made it to
28,250’

Edmund Hillary and Tenzing Norgay (Namgyal Wangdi) reached the

summit on May 28th 1953

Ventilatory response to O2
Adaptation to high altitude!
One of the first defences against hypoxia is an increase in 60 If ventilation rises a little, PCO2
Ventilation (litres per minute)

alveolar ventilation.! falls and [H+] in the CSF and at the

50
However, the immediate ventilatory response to a fall in central chemoreceptors falls and this
arterial PO2 is not very great until PO2 falls below about 8 kPa 40
acts as a ‘brake’ to ventilatory drive.
(60 mmHg):! The net affect is very little effect
30 until the hypoxic stimulus is strong!

20

10

0
0 4 8 12 16
Arterial PO2 (kPa)

Sudden exposure to altitudes up to about 3000m are associated with acute exposure to altitude!
little change in ventilation. !
If ventilation and metabolism are unchanged then with reduced
3000 m! sea level!
inspired PO2, alveolar and arterial PO2 will fall. !
Remember:! 3600 m!

alveolar and arterial PCO2 ∝ CO2 production (unchanged)!

! ! ! ! alveolar ventilation (unchanged)!
∴ acute exposure to altitudes up to 3000 m !
! !⇒ low arterial PO2 and normal arterial PCO2!
Above about 3000 m ventilation increases.!
! !⇒ low arterial PO2 and low arterial PCO2!

1 mmHg = 0.133 kPa 1 kPa = 7.5 mmHg

 The oxygen cascade
at different altitudes!
note: the ‘steps’ are
reduced at altitude
so the reduction in
capillary and mixed
venous PO2 is not
great as the fall in
0! 3000! 6000! altitude , m! moist inspired PO2
(fortunately!)!

Mean values of alveolar PO2 (line A)and PCO2 (line C) for 30 subjects
exposed acutely to altitude. The dashed red lines B and D show alveolar
PO2 and PCO2 if ventilation had not changed.!
Gradwell, 2006 in Ernsting’s Aviation Medicine

Alveolar PCO2 and PO2 during acute & chronic exposure to different
If the subject remains at altitude over the next few days ventilation altitudes! acute!
gradually increases ! !
alveolar PO2 increases* and PCO2 falls.!
sea level!
chronic!
?mechanism of the increased ventilation?!
During acclimatisation bicarbonate is transported out of the CSF and
the kidney excretes more bicarbonate so that the CSF and arterial blood
pH returns to normal and hence initial inhibition of the central
chemoreceptors by low PCO2 / alkalosis is removed.! Ventilation ↑:
PO2 rises
However, other mechanisms probably contribute to the ventilatory PCO2 falls
acclimatisation!
*compared to following acute exposure; it remains below the sea level
value !

•  Hypoxic ventilatory response, HVR, variable but

initially ventilation is usually: Over the next few days:
little changed below 3000 m •  Hyperventilation starts or is enhanced.
increased at altitudes above 3000 m •  Increased excretion of HCO3- by kidneys
•  Alkalosis due to reduction in PCO2 resulting from any •  Decreased HCO3- in CSF.
increase in ventilation. •  Increased 2,3-DPG (diphosphoglycerate*) in RBC.
•  Increased resting and submaximal heart rate. •  Increased haemoglobin concentration (stimulated by
•  Similar or slightly reduced stroke volume. erythropoietin, EPO)
•  Increased resting and submaximal CO.
*aka 2,3 BPG (biphospoglycerate)
CO2 + H2O ⇔ H2CO3 ⇔ HCO 3- + H+
 The increased [Hb] is
useful in increasing the
oxygen content of the
blood at altitude but the

viscosity centistokes!
increased viscosity
increases TPR and the
work of the heart. !

When Hct > 55% the

disadvantages probably
outweigh the
advantages,!

Haematocrit (Hct) %!

↓PaCO2 !

•  Heart rate remains elevated.

↑2,3 DPG
•  Decreased stroke volume and CO may fall.
The increased 2,3 DPG reduces affinity (aiding O2
unloading in the tissues) but the low PaCO2 increases
the affinity (aiding O2 uptake in the lungs). ! •  Increased capillarity of tissues.
At most altitudes these two effects balance out and
there is little change in affinity. !
•  Increase in mitochondria and aerobic enzymes.
At extreme altitude the very low PCO2, due to greatly
increased ventilation, increases the affinity of Hb for
O2 and aids uptake of O2 in the lungs.! •  Increased myoglobin.

•  Loss of lean tissue mass.

There may be difference between people born at low

altitude who move to live at high altitude and native
highlanders in the way they respond to living at altitude:
 Acute Mountain Sickness!
- probably due to combination of hypoxia and alkalosis!

•  AMS: Acute mountain sickness - most common. Occurs especially with rapid ascent to altitudes > 2500 m,
30-50% of people above 12,000ft (3,660m) usually disappears spontaneously after 1 - 3 days.
Symptoms are exacerbated by exercise!

•  HAPE: High-altitude pulmonary edema - reverses if !headache!

descend but potentially fatal. !fatigue!
!dizziness!
•  HACE: High-altitude cerebral edema - potentially fatal
and requires immediate diagnosis and treatment. !insomnia!
!loss of appetite!
•  CMS: Chronic Mountain Sickness
!nausea!

High Altitude Pulmonary Edema (HAPE)! High Altitude Cerebral Edema (HACE)!
•  s! evere breathlessness (dyspnoea)! ! !confusion!
•  !orthopnoea (dyspnoea worse lying down)!
•  !cough! ! !ataxia!
•  !cyanosis! ! !irrationality!
•  !crackles on auscultation!
•  !cough up pink frothy fluid! ! !hallucinations!
! !clouding of consciousness!
probably related to hypoxic vasoconstriction of
pulmonary vessels. This raises pulmonary arterial ! !coma!
pressure. If the constriction is uneven ⇒ leakage from mechanism is uncertain!
less constricted vessels.!
immediate descent essential!
life threatening - requires immediate descent!

Chronic Mountain Sickness = Monge’s disease! 210 climbers have died (up
to end of 2008) attempting
occurs in long-term high altitude residents. mostly affects the Everest summit!
young or middle-aged men! Many of them remain there!
!cyanosis!
About 20% of these had
!fatigue! reached the summit!
!headaches, dizziness, somnolence!
Main causes of death:!
!reduced exercise capacity! !avalanches,,!
!marked polycythaemia! !falls!
other causes include: !
!severe hypoxia! !frostbite, !
!finger clubbing! !pulmonary oedema,
!cerebral oedema,
best treated by moving to live at lower altitude! frostbite! !hypothermia, !
!pneumonia!
Exercise at high altitude: Reduced capacity for aerobic respiration!
Race Times at Altitude (% Sea Level)

150 2-3 hours

3,800 ml/min

2-5 min
115

1,100 ml/min
100 <2 min
95
1000 2000 3000 4000 5000
approx values for 70 kg man Altitude

.
“Altitude training” Effect on VO2 max of altitude and sea level training in
two groups highly trained middle distance runners
Does it work?
!Potential advantage: !
!Increased O2 carrying capacity related to polycythaemia!
!but!
!Ability to exercise is reduced at altitude, therefore training
intensity reduced.!

!No evidence that training at altitude significantly improves sea-

level performance (eg. see next slide). !

!This is probably because the advantage of increased oxygen

carrying ability is offset by the disadvantage of the less intense
training that is possible at altitude.! Group 1 sea level for 3 weeks then altitude for 3 weeks
Group 2 altitude for 3 weeks then sea level for 3 weeks

There is some evidence that “Live high - train low” (sleep in

hypoxic tent, train in normoxia) may improve sea level
performance.

Provides the benefits of altitude adaptations without reducing

training intensity.