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