High AltitudeHealth Effects
Dr.Demet Demircioğlu
High Altitude
• International Society for Mountain Medicine:
• High altitude = 1,500–3,500 m • Very high altitude = 3,500–5,500 m• Extreme altitude = above 5,500 m
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
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
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
UV Increases at Altitude
Water Vapor Decreases at Altitude
Oxygen and HealthThe 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
O2 - Air to Mitochondria – ATPThe 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
Oxygen from Air to Blood
O2 into blood, then into RBC,on to hemaglobin – normally > 97 % sat
RBCs in vessel Hemaglobin molecule
O2 - Lung to Circulation to Tissue
O2 into Tissues, Cells, Mitochondria
O2 Facts
• rest O2 consumption – 250 ml / minute
• 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
Problem with Altitude – Low 02
Hypoxemia and Altitude
HypoxemiaHinge Points
Oxygen Carrying
• Normal O2 sat > 97
• 94 %– ppO2 blood - 70
– Humans work to keep O2 at or above
• 90 %– Below O2 content drops
dramatically
– Hypoxia can occur – low energyproduction
• 80 %– Cognitive dysfunction
– Other organ dysfunction
Altitude O2 Sat
• 2000 m sat less than 94%
• 3500 m sat less than 90 %
• 5500 m sat less than 80 %
Oxygen Content – ppO2
AcclimatizationAdjusting 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)
AcclimatizationImmediate
• Lung– increased respiratory rate
– increased tidal volume
– Pulmonary artery vasoconstriction - V/Q
– increase O2 in alveoli - blood
• Cardiovascular– increased heart rate /
contraction
– increased BP (10mm Hg)/ venoustone
– increase DO2• DO2 = CO x O2 content blood
(hgb x %sat)
• CO = HR x stroke volume
• Cerebral
– Increase flow (up to 24 % at 4000 m)
– More O2 to highly O2 dependant brain
• Digestive– Decreased appetite, digestion
– decreased energy demand for taxed body
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
AcclimatizationLong Term, Weeks – 2 mos
• Polycythemia– Kidney puts out erythropoietin
– stimulates bone marrow to make more RBCs
• Increased RBC mass– More Hgb
• Increased muscle capillaries– More DO2 to exercising
muscles
• Increased myoglobin– Muscle protein holds, stores
O2
• Mitochondria - aerobic
– Decrease number
– More efficient O2 use
• Increased anaerobic metabolism
– Outside mitochondia
– Increased efficiency
• Heart– HR stays higher
– BP comes down
AdaptationGenerations
• 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
AdaptationGenerations
• 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)
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
What to Expect at AltitudeNormal Acclimatization Response
• Fatigue
– Common
– Lasts up to 48 hours
– Due to energy availability
• Mild Shortness of Breath
– Due to increased need for ventilation
– 2 – 4 days
• Mildly increased HR, BP
– Due to increased DO2
– BP Up to a week (10 mmHg)
– HR stays up
• Increased diuresis
– Up to 4 days
• Poor performance– Mental but especially physical
– Up to a week
• Weight loss
– Diuresis
– Decreased appetite
• Disturbed sleep– Periodic breathing
– Due to need to hyperventilate, and subsequent alkalosis
USArmyInstitute for Environmental Medicine
• 4,000 ft (1200 m) – physical performance
• 8,000 ft (2440 m) – cognitive performance
• 10,000 ft (3,050 m) - judgement
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)
Altitude SicknessFailure 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
AMI – Risk Above 2500 m (8200 ft)
Cause:•lung, cardiovacular, renal, energy
•stress
•Increased cerebral flow
• Symptoms– Fatigue
– HA
– Light headedness
– Anorexia, nausea, vomiting
Disturbed sleep
• No lab / Xray tests
Timing / treatment
• 4 – 6 hours after arrival
• Worse after first night
• Resolves two days
• Treatment– NSAIDs/tylenol
– Acetizolamide (48 – 72 hrs)
– Dexamethasone (48 – 72 hrs)
– If does not resolve descend
– If severe – oxygen 2 – 4 l/min
Nasal O2
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
HACE / HARHAbove 4500 m (14,760 ft)
HACE
• Cause– Leak from cerebral blood
vessels – brain swelling– microhemorrhage
• Sxs– Start 6 – 12 hrs– Confusion– Impaired motor fxn /gait– Stupor to coma
• Tests– MRI
• Treatment– Descend ASAP– Oxygen– Hyperbaric oxygen– dexamethasone
HARH
• Similar to HACE
– Retinopathy
– microhemorrhage
Picture Brain Edema
Portable Hyperbaric Chamber
HAPEAbove 4500 m (14,760 ft)
• Severe pulmonary Hypertension
• Some areas pulmonaryvascular bed overperfused
• Blood vessel injury
• Fluid leak into lung
• Lung edema – water
– Worsens gas exchange
Pathophysiology Clinical
• 2 – 4 days after arrival
• SOB
• Cough
• Hemoptysis
• Dx
– Crackles
– Xray
PHTN
HAPE Treatment
• Oxygen
• Descent
• Hyperbaric chamber
• Positive Pressure Ventilation
• B – agonist inhalers
• Pulmonary vasodilators– Nifedipine
– sildenafil
Chronic Mountain IllnessMonge’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
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)
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)
Risk by Medical IllnessCan’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
RecommendationsGoing 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
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
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
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
Above 3500 m
• If rapid significant risk AS
– Acetazolamide
– Decadron prophylaxis
– O2
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
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
O2 requirement2000 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
SAS2000 m (6500 ft)
• Worse at altitude
• 1500 m – diamox
• 2500 m - O2 with CPAP
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
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)
Water
Dehydration
– At 6000 m or feet – loose twice as much water• Water through skin and
breathe
– Hypohydration – increases risk of AMS• 1999 – Basnyat – AMS risk
increases by 60 %
• Less than 3 Liters per day
– Hyperhydration – increases riskfor AMS/HAPE/HACE• 2009 – Richardson – increased
risk
• Above 4500 m
Symptoms
• Lack of perspiration
• Overheating
• Headache
• Light headed
• Fatigue
• Dark (concentrated urine)
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
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
Sun UVB &UVA
Altitude
• For every 1000 ft altitude 4– 8 % more UVB exposure
• So at 8000 ft – more than 30 % more exposure
Other effectors• 85% increase from snow reflection
• 25% increase from white-water reflection
• 50 % increase from water reflection• 80% of UV rays pass through cloud• 20% from sand and grass
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
UV Exposure Skin
Adverse Effects
• Burn
• Aging
• Skin cancer
Recs
• Micro zinc oxide 5 % - only ingredient that blocks all of UVA and UVB
• SPF – 30 at least– Sun Protection Factor
• 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
UV Exposure Eye
Complications
• Acute– Photokeratitis - corneal burn
– snow blindness
– Photoconjunctivitis –conjunctival burn
• Chronic– Pterygium – conjunctival
growth
– Cataracts
– retinopathy
Guidelines – eye wear• 99-100% UV absorption• Polycarbonate or CR-39 lens
(lighter, more comfortable than glass)
• 5-10% visible lighttransmittance “glacier glasses”
• Large lenses that fit close to the face
• Wraparound or side shielded to prevent incidental light exposure
• If out more than 30 minutes
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
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
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