John Muir found being in the mountains calming and spiritual. High altitude was defined as between 1,500-3,500 meters and extreme altitude was above 5,500 meters. The body acclimatizes to high altitude through immediate responses like increased breathing and heart rate, intermediate responses over days like increased red blood cells, and long term responses over weeks like growth of lung capillaries and more efficient use of oxygen. Generations that live at high altitude like Tibetans have developed genetic adaptations through natural selection that augment the acclimatization process.

2. John Muir
• “Thousands of tired, nerve-shaken, over-civilized
people are beginning to find out going to the
mountains is going home ...”
• “… the alpenglow, to me the most impressive of
all the terrestrial manifestations of God … the
mountains seemed to kindle to a rapt, religious
consciousness, and (the beholder) stood hushed
like devout worshippers waiting to be blessed.”

3. High Altitude
Health Effects
the good, the bad and the interesting
J Pat Herlihy MD
Jph@houstonlungdocs.com

4. High Altitude
• International Society for Mountain Medicine:
• High altitude = 1,500–3,500 m (4,900–11,500 ft)
• Very high altitude = 3,500–5,500 m (11,500–18,000 ft)
• Extreme altitude = above 5,500 m (18,000 ft)

5. City Altitude
The 10 highest cities in the world
1. Lhasa, Tibet, China 12,002 ft./3658 m.
2. La Paz, Bolivia 11,910 ft./3630 m.
3. Cuzco, Peru 11,152 ft./3399 m.
4. Sucre, Bolivia 9331 ft./2844 m.
5. Quito, Ecuador 9249 ft./2819 m.
6. Toluca, Mexico 8793 ft./2680 m.
7. Bogotá, Colombia 8675 ft./2644 m.
8. Cochabamba, Bolivia 8390 ft./2557 m.
9. Addis Ababa, Ethiopia 7900 ft./2408 m.
10. Asmara, Ethiopia 7789 ft./2374 m.

6. Some large cities (and Aspen) at high altitude
Mexico City 7350 ft./2240 meters
Johannesburg 5750 ft./1750 meters
Nairobi 5,500 ft./1660 meters
Denver 5,300 ft./1610 meters
Guatemala City 5,000 ft./1530 meters
Aspen 8,000 ft./2440 meters

7. Peak Altitude Location
The Seven Summits
Mount Everest 29,035 ft./8850 m. Asia
Mount Kilimanjaro 19,563 ft./5963 m. Africa
Mount McKinley 20,320 ft./6194 m. North America
Puncak Jaya 16,023 ft./4884 m. Australia/Oceania
Vinson Massif 16,066 ft./4897 m. Antarctica
Mount Elbrus 18,510 ft./5642 m. Europe
Aconcagua 22,841 ft./6962 m. South America

8. Highest Ski Resorts
USA World
• Breckenridge, CO • Chalaltaya, Bolivia
– 12,840 ft, 3914 m – 17,388 ft, 5300 m
• Loveland, CO
– 12,700 ft, 3870 m • Gulmaq, India
– 13,058 ft, 3980 m
• Arapahoe Basin, CO
– 12,472 ft, 3801 m
• Tachal, Iran
• Winter Park, CO – 12,631 ft, 3850 m
– 12, 060 ft, 3676 m

9. High Altitude Environment
• Air density – key factor for health related issues
• Air pressure (barometric) lessens as altitude increases
– As altitudes increases, less air above pressing down
– Think ocean pressure
• Pressure at bottom higher from weight of water above

10. Air Pressure - Altitude
• Less air pressure
– less dense air – “thin air”
– Air holds less molecules per area
– Individual gas’ pressure is less
• 3 important consequences:
– Lower number of oxygen molecules / area (less ppO2)
– Lower number of water molecules / area (lower humidity)
– Less and thinner air above to shield from harmful sun rays

11. High Altitude Environment
Health
• Oxygen
– Lower air pressure – lower oxygen content in air
– Major effect for health
• Humidity
– Lower air pressure – lower water content in air
– Dehydration risk
• Sun
– less atmospheric protection from
– More UV ray exposure

12. UV Increases at Altitude

13. Water Vapor Decreases at Altitude

14. Graphic of Altitude and ppO2

15. Oxygen and Health
The Quick Tour
• Oxygen needed for production of ATP
– Key energy molecule of the body
– Made in every cell of the body - mitochondria
– Needed for function and even survival of cells/body
– Hypoxia – tissues don’t have enough O2
– Can’t produce normal quantities of energy
• Body can produce ATP without O2
– anaerobic metabolism or cellular anaerobic respiration
– 13 times less efficient

16. O2 - Air to Mitochondria – ATP
The Quick Tour
• Lungs’ function – air (O2) to blood
• Red blood cell (RBC) – carries bulk of O2 in blood
• Circulatory system - carries O2 rich blood to
tissues
• Mitochondria – uses O2 to manufacture ATP, the
energy molecule

17. Oxygen from Air to Blood

18. O2 into blood, then into RBC,
on to hemaglobin – normally > 97 % sat
RBCs in vessel Hemaglobin molecule

19. O2 - Lung to Circulation to Tissue

20. O2 into Tissues, Cells, Mitochondria

21. Cell

22. Mitochondria

25. ATP
Adenosine Triphosphate

26. Fun O2 Facts
• Ave rest O2 consumption – 250 ml / minute
• Ave rest amount of O2 from blood – 25 %
• Healthy adult minute ventilation 5 – 8 l/min
• Vt 500 ml, 7 ml/ kg, RR 12 – 20 bpm
• VO2 max 45 ml/kg/minute
• VO2 max 3.5 l / minute

27. Graphic of Altitude and ppO2

28. Problem with Altitude – Low 02

29. Hypoxemia and Altitude

30. Hypoxemia
Hinge Points
Oxygen Carrying Altitude O2 Sat
• Normal O2 sat > 97
• 94 % • 2000 m sat less than 94%
– ppO2 blood - 70 – 6500 ft
– Humans work to keep O2 at or
above
• 90 %
– Below O2 content drops • 3500 m sat less than 90 %
dramatically – 11,500 ft
– Hypoxia can occur – low energy
production
• 80 %
– Cognitive dysfunction • 5500 m sat less than 80 %
– Other organ dysfunction – 18,000 ft

31. Oxygen Content – ppO2

32. Acclimatization
Adjusting to Thin Air, Low Oxygen
• Begins 1500 m (5000 ft) to 2000 m (6500 ft)
• Intensity depends upon how high, how fast
“hypoxic stress”
• Three phases
– Immediate
– Intermediate (days)
– Long term (weeks to 2 mos)

33. Acclimatization
Immediate
• Lung • Cerebral
– increased respiratory rate – Increase flow (up to 24 % at
– increased tidal volume 4000 m)
– Pulmonary artery – More O2 to highly O2
vasoconstriction - V/Q dependant brain
– increase O2 in alveoli - blood
• Cardiovascular • Digestive
– increased heart rate / – Decreased appetite, digestion
contraction – decreased energy demand
– increased BP (10mm Hg)/ venous for taxed body
tone
– increase DO2
• DO2 = CO x O2 content blood
(hgb x %sat)
• CO = HR x stroke volume

34. Ventilation Perfusion Matching
where less air less blood flow

35. Acclimatization
Intermediate - Days
• Kidney
– bicarbonate diuresis for acid base balance
– Hyperventilation causes blood alkalosis
– Kidney compensates
• Pulmonary
– Ventilation increase and V/Q matching continue for up to one
week
– PHTN continues (mean 25 mmHg – mild)
• 2,3 DPG
– Molecule in RBC that allows Hgb to unload O2 easier into the
tissues

36. Acclimatization
Long Term, Weeks – 2 mos
• Polycythemia • Mitochondria - aerobic
– Kidney puts out erythropoietin – Decrease number
– stimulates bone marrow to
make more RBCs – More efficient O2 use
• Increased RBC mass • Increased anaerobic
– More Hgb metabolism
• Increased muscle capillaries – Outside mitochondia
– More DO2 to exercising – Increased efficiency
muscles • Heart
• Increased myoglobin – HR stays higher
– Muscle protein holds, stores – BP comes down
O2

37. Adaptation
Generations
• Genetic selection of advantageous traits for altitude
• Three populations studied
– Andeans
• Above 4000 m (13,000 ft)
• Increased HGB
– Tibetans and Nepalese
• Above 4000 m (13,00 ft)
• Increased ventilation (breathing)
• Increased blood vessels, and circulatory performance
• Cellular energy – anaerobic and efficient
– Amhara people Ethiopia
• Above 3500 m (11,500 ft)
• Normal ventilation
• Normal blood vessels
• Cellular energy – anaerobic and efficient

39. Adaptation
Generations
• Adapted populations have a different set of genes
(natural selection) that essentially, augment
acclimatization
– U College London
– U of Colorado
– Mayo
• Different level of expression of hypoxia beneficial genes
– 2010 – Science and PNAS - multinational team, led by U
College London, Hugh Montgomery
• Tibetans at 15,000 ft have a variant of EPAS1 gene (controls HIF-1)
• HIF = Hypoxia-Inducible Factor (discovered 1995)

40. Very Exciting
• HIF – Hypoxia Inducible Factor
– Discovered 1992
• Hopkins team investigating erythropoeitin
– “transcription factor”
– Turns on hundreds of genes helpful to acclimatization
• All three populations of high altitude people have
upregulated HIF pathway
• Genes turned on by altitude can help understand hypoxia
tolerance and develop therapies
• Important in cardiac and pulmonary disease

42. What to Expect at Altitude
Normal Acclimatization Response
• Fatigue • Increased diuresis
– Common – Up to 4 days
– Lasts up to 48 hours • Poor performance
– Due to energy availability – Mental but especially physical
• Mild SOB – Up to a week
– Due to increased need for • Weight loss
ventilation
– Diuresis
– 2 – 4 days
– Decreased appetite
• Mildly increased HR, BP • Disturbed sleep
– Due to increased DO2
– Periodic breathing
– BP Up to a week (10 mmHg)
– Due to need to
– HR stays up hyperventilate, and
subsequent alkalosis

44. USArmy
Institute for Environmental Medicine
• 4,000 ft (1200 m) – physical performance
• 8,000 ft (2440 m) – cognitive performance
• 10,000 ft (3,050 m) - judgement

45. Physical performance
• After acclimatization (2 weeks) level of fitness
performance depends upon altitude
– 1% loss for every 100m above 1500 m
• 90 % at 2500 m (8,200 ft)
• 75 % AT 4000 m (13, 100 ft)
• 65 % AT 8000 m (26, 240 ft)

46. Altitude Sickness
Failure of Acclimatization
• Acute mountain Illness
• Sleep disordered breathing
• HAPE – high altitude pulmonary edema
• HACE – high altitude cerebral edema
• HARH – high altitude retinal hemaorrhage
• Chronic Mountain illness

47. AMI – Risk Above 2500 m (8200 ft)
Cause: Timing / treatment
•lung, cardiovacular, renal, energy
•stress
•Increased cerebral flow
• Symptoms • 4 – 6 hours after arrival
– Fatigue • Worse after first night
– HA • Resolves two days
– Light headedness
• Treatment
– Anorexia, nausea, vomiting
– NSAIDs/tylenol
– SOB
– Acetizolamide (48 – 72 hrs)
– Disturbed sleep
– Dexamethasone (48 – 72 hrs)
• No lab / Xray tests – If does not resolve descend
– If severe – oxygen 2 – 4 l/min

48. Nasal O2

49. Sleep Disordered Breathing
Above 3500 m (11,500 ft)
• Periodic breathing
– Periods of rapid breathing during sleep
– Cycle between normal shallow ventilation of
sleep, hyperventilation to maintain O2 sat
• Can disrupt deep sleep
– Frequent arousals
– Less time in REM – deep sleep
• Oxygen can help
• Resolves 2 – 3 days

50. HACE / HARH
Above 4500 m (14,760 ft)
HACE HARH
• Cause • Similar to HACE
– Leak from cerebral blood
vessels – brain swelling – Retinopathy
– microhemorrhage – microhemorrhage
• Sxs
– Start 6 – 12 hrs
– Confusion
– Impaired motor fxn /gait
– Stupor to coma
• Tests
– MRI
• Treatment
– Descend ASAP
– Oxygen
– Hyperbaric oxygen
– dexamethasone

51. Picture Brain Edema

52. Portable Hyperbaric Chamber

53. HAPE
Above 4500 m (14,760 ft)
Pathophysiology Clinical
• Severe pulmonary • 2 – 4 days after arrival
Hypertension • SOB
• Some areas pulmonary • Cough
vascular bed overperfused • Hemoptysis
• Blood vessel injury • Dx
• Fluid leak into lung – Crackles
• Lung edema – water – Xray
– Worsens gas exchange

54. Ventilation Perfusion Matching
where less air less blood flow

55. PHTN

58. HAPE Treatment
• Oxygen
• Descent
• Hyperbaric chamber
• Positive Pressure Ventilation
• B – agonist inhalers
• Pulmonary vasodilators
– Nifedipine
– sildenafil

59. Chronic Mountain Illness
Monge’s Disease
Above 3000 m (9,840 ft)
• Polycythemia
– Hgb > 20
• Chronic PHTN
• SXs
– Poor mental function
– Poor organ function
– Total body edema
• Treatment
– descend

61. Risk of Altitude Sickness
• Risk by altitude
– AMI - above 2500 m 20 %, above 4500 m 50 %
• Sleep disordered breathing 3500 m
– HAPE – above 4500 m 5 - 10 %
• slow ascent from 2000 m only 1 – 2 %
– HACE – above 4500 m 1 – 2 %
– HARH – above 4500 m 1 - 2 %
– Death zone – above 8000 m – acclimatization not
possible, survival – hours, days max
– Adaptation – not above 6000 m, 19,700 ft
– Everest- 8850 m, 29000 ft
• Base camp 5100 m (16, 728 ft) – 5400 m (17, 712 ft)

62. Risk of Altitude Sickness
• Risk by speed
– Above 3000 m (9800 ft)
• No more than 500 m /day if low risk AMI
• No more than 350 m / day if high risk AMI
• Every two days rest for a day
• If ascend high quickly, acetazolamide and decadron
• Risk by time at altitude – length of hypoxic stress
– Pikes peak (4,270 m, 14,000 ft) – low rate
– Up to 4000m (13, 100 ft) hours
• Risk by sleeping altitude
– Above 2750 m, 9,000 ft
– Associated with hypoxic episodes
– Hike high sleep low
• Pre acclimatization prior stay at altitude - lowers risk
– 4 days
– Within months
• Risk by history of AS – at risk if go above 2500 m (8200 ft)

63. Risk by Medical Illness
Can’t Compensate for Low ppO2
• Lung disease
• Cadiovascular disease
– CAD
– CHF
• Anemia
– Hct < 30, Hgb < 10
• Hemaglobinopathy
– Sickle cell, etc.; 2,3 GDP deficiency
• Sleep apnea

64. Recommendations
Going to Altitude – Above 2000 m
• People are highly variable in acclimatization
– Genetically determined (low PDP2 gene
expression – intolerant of altitude)
– Not a function of fitness
– Older age (> 50) may be mildly protective against
Altitude Sickness
– Women slightly higher risk
– Underlying diseases:
• Lung disease
• Heart disease

65. Risk
• Can’t asses with current technology
• Hypoxic exercise – not predictive
• Future gene array or hypoxic HIF levels
• For now:
• Altitude
• History of AS
• Underlying medical conditions

66. Recommendations
• If history of AMS / travel above 2500 m (8200 ft)
ft – acetazolamide
– 24 hrs before, and for 48 hrs into stay
– 250 mg bid
• First night sleep at less than 9000 feet (2750 m)
– (ARC – UC)
• Rest for 2 – 4 days
– Vigorous exercise may prompt AMI
• Creating tissue hypoxia
• Gradual activity increase over week
• Signs of AMI – 500 - 1000 m descent

67. Recommendations
• Alcohol, sleeping pills, other respiratory
depressants – avoid 2 days to one week
• Caffeine – do not cold turkey – a respiratory
stimulant
• Avoid salty – increases BP
• No tobacco – CO impairs O2 transport
• Carbohydrates – best fuel for high altitude
– Helps aerobic / anaerobic metabolism

68. Above 3500 m
11,500 ft
• If rapid significant risk AS
– Acetazolamide
– Decadron prophylaxis
– O2

69. Altitude tolerance - common cardiovascular and
pulmonary diseases
Travel to altitudes above 2000 m inadvisable:
• Cardiovascular diseases
– Within 3 months of myocardial infarction, stroke, ICD implantation,
thromboembolic event – within 3 weeks
– Unstable angina pectoris
– Before planned coronary interventions
– Heart failure, NYHA class >II
– Congenital cyanotic or severe acyanotic heart defect
• Pulmonary diseases
– Pulmonary arterial hypertension
– Severe or exacerbated COPD (GOLD stage III–IV)
– FEV1 <1 liter
– CO2 retention
– Poorly controlled asthma

70. Travel to altitudes of 2000-3000 m permissible:
• Cardiac diseases
– asymptomatic or stable CAD (CCS I–II)
– Stress ECG normal up to 6 METs
– Normal performance capacity for age
– Blood pressure under good control
– No high-grade cardiac arrhythmia
– No concomitant illnesses affecting gas exchange
• Pulmonary diseases
– Stable COPD or asthma under medical treatment, with adequate reserve
function for the planned activity
• For travel to altitudes above 3000 m:
– Evaluation by a specialist in altitude medicine and physiology
ICD, implantable cardiac defribrillator; NYHA, New York Heart Association; COPD, chronic
Obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease;
FEV1, forced expiratory volume in 1 second; CHD, coronary heart disease; CCS, Canadian
Cardiovascular Society; MET, metabolic equivalent of task

71. O2 requirement
2000 m (6500 ft) – 3000 m(9840 ft)
• O2 Sat greater than 95 % - OK
• O2 Sat less than 92 % - need O2
• Between 92 – 95 % assesment
– If concurrent lung / heart disease – O2
– Rule is 2 liters
• if no O2 2 liters / min
• If O2 2 liters / min above base - chronic lung disease

72. SAS
2000 m (6500 ft)
• Worse at altitude
• 1500 m – diamox
• 2500 m - O2 with CPAP

73. Pregnancy
• High altitude communities
– Lower birth weights, though developmentally OK
– Higher incidence of PIH, preeclampsia, eclampsia
• Physiology
– Between 2500 and 3000 m, in utero Hgb increases
• Recs
– Up to between 2500 (8,200 ft) and 3000 (10,000
ft) safe

75. Pediatrics
• Younger children (less than 8 y.o.)
progressively more at risk (up to 4 x) for
hypoxia and altitude sickness
– Limited ability to compensate
• Teens twice the risk
• Recs
– Absolutely no child above 3500 m (11,500 ft)
– Young children not above 3000 m (10,000 ft)
– Teens acclimatization and great care above 3500
m (10,000 ft)

76. Water
Dehydration Symptoms
– At 6000 m or feet – loose twice • Lack of perspiration
as much water
• Water through skin and • Overheating
breathe
– Hypohydration – increases risk
• Headache
of AMS • Light headed
• 1999 – Basnyat – AMS risk
increases by 60 % • Fatigue
• Less than 3 Liters per day
• Dark (concentrated urine)
– Hyperhydration – increases risk
for AMS/HAPE/HACE
• 2009 – Richardson – increased
risk
• Above 4500 m

77. Temperature
• Drops 3.5 degree F for every 1000 ft
• Drops 6.5 degree C for every 1000 m
• Contributes to decreased humidity at altitude

79. Water
Hydration Recs
• Usual daily fluid intake
– 8, 8 oz glasses water /day
– ½ body weight (lbs) in ozs
• Twice usual intake
– 3 – 5 Liters / day
• Key to start day, exercise hydrated
– O/N lose hydration
– Data is that most altitude hikers start hypohydrated
– 16 ozs to start
– Altitude exercise 8 ozs every 20 minutes

80. Sun
UVB &UVA
Altitude Other effectors
• For every 1000 ft altitude 4 • 85% increase from snow reflection
• 25% increase from white-water
– 8 % more UVB exposure reflection
• 50 % increase from water reflection
• 80% of UV rays pass through cloud
• So at 8000 ft – more than • 20% from sand and grass
30 % more exposure reflection - and 40% when wet
• 15% reflection from concrete
buildings
• 50% can be reflected into shaded
areas
• 50% UVB and 80% UVA passes
through the upper 50cm of water

82. UV Exposure
Skin
Adverse Effects Recs
• Micro zinc oxide 5 % - only
ingredient that blocks all of UVA
• Burn and UVB
• Aging • SPF – 30 at least
– Sun Protection Factor
• Skin cancer • amount of UV radiation required
to cause sunburn on skin with the
sunscreen on, as a multiple of the
amount required without the
sunscreen
• how long one can stay in the sun
• If in water or sweating – water
resistant
• If in sun more than 30 minutes
• Fresh screen

83. UV Exposure
Eye
Complications Guidelines – eye wear
• Acute • 99-100% UV absorption
– Photokeratitis - corneal burn
• Polycarbonate or CR-39 lens
(lighter, more comfortable
– snow blindness than glass)
– Photoconjunctivitis – • 5-10% visible light
conjunctival burn transmittance “glacier glasses”
• Chronic • Large lenses that fit close to
the face
– Pterygium – conjunctival
growth
• Wraparound or side shielded
to prevent incidental light
– Cataracts exposure
– retinopathy • If out more than 30 minutes

86. High Altitude Living – Healthy
Colorado – Highest State
• J of Epi and Community Health - 2011
– Colo – lowest death rate from cardiovascular disease
• Lower rate of HTN
– Colo – lowest death rate lung and colon CA
• J of Epi and Community Health – 2004
– Greece - Lower rate of total and cardiovascular deaths at altitude
• Robert Wood Johnson foundation
– Lowest rate of obesity USA – Colorado
– 19.8 %
• 7 / 10 counties in US with greatest longevity
– In Colorado – average altitude

87. High Altitude Living - Unhealthy
• J of Epi and Community Health - 2011
• High rate of skin cancer Colo
• Colorado – always in top 10 states suicide rate
• Similar data from around the world
• Perry Menshaw U of Utah, Brain Institute
– Altitude above 6000 ft is associated with suicide
rates

88. Mechanisms
• CV health
– altitude good for blood vessels and circulation
– Vessel growth and plasticity
• Vit D (from sunlight) may protect against colon
and other cancers
• COPDers (smokers) do not tolerate Colo
• Hypoxemia may promote anxiety / depression

89. Athletes
• U of Utah, UC Colo
Springs, Australia, Switzerland, Norway
• blood doping (1980s), epo (1990s)– 17 %
improvement in speed and endurance
• Live high train low – now the standard
– live 2500 m or sleep in low O2 environments (10
hours)
• Trigger better O2 use
– train low 1250 m, or use supplemental O2
• To optimally work muscles
– Improvements average 2 – 3 % - some more
– Improvements last 2 weeks

90. Live Low – Sleeping Tent

91. Aspen
• Altitude
– 2450 m (8,000 ft)
• Baromatric pressure
– 739 mm hg
• O2 content
– ppO2: 112
– 75 % sea level