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