High Altitude

Epidemiology

  • xxx

Normal Physiology at High Altitude

Partial Pressure of Oxygen (PIO2)

  • PIO2 = FIO2 x (Pb – 47 mmHg)
    • FIO2: fraction of oxygen in inspired air
      • FIO2 remains constant at 20.94% at all altitudes (even into the upper troposphere) -> therefore, PIO2 is related directly to the barometric pressure (Pb)
    • Pb: barometric pressure (also known as Patm = atmospheric pressure)
      • Barometric pressure significantly decreases with altitude
      • Barometric pressure is less significantly decreased by lower temperature, higher latitude, and inclement weather, and during winter: these latter factors are more influential at altitudes over 9200 ft (2800 m)
    • Water Vapor Pressure at 37°C: 47 mm Hg

Relationship Between Altitude, Barometric Pressure, and Arterial pO2 (in Residents Living at Altitude)

  • Altitude of 5400 ft (1646 m): Pb = 630 mm Hg
    • pCO2: 35.6 mm Hg
    • pO2: 73 mm Hg

Relationship Between Altitude, Barometric Pressure, and Arterial pO2 (with Acute Exposure to High Altitude)

  • Altitude of 9219 ft (2810 m): Pb = 543 mm Hg
    • pCO2: 33.9 mm Hg
    • pO2: 60 mm Hg
  • Altitude of 12,008 ft (3660 m): Pb = 489 mm Hg
    • pCO2: 29.5 mm Hg
    • pO2: 47.6 mm Hg
  • Altitude of 15,240 ft (4700 m): Pb = 429 mm Hg
    • pCO2: 27.1 mm Hg
    • pO2: 44.6 mm Hg

Development of Hypobaric Hypoxia

  • At Sea Level: there is a large oxygen pressure gradient for oxygen between inspired air and the tissues
  • At Altitude: there is a decreased PIO2 with decreased oxygen pressure gradient
    • With Exertion at High Altitude, the Additional Element of Increased Oxygen Consumption Can Result in Tissue Hypoxia (Hypobaric Hypoxia)

Acclimatization to High Altitude

General Comments

  • Definition of Acclimatization: normal compensatory responses to hypobaric hypoxia -> with the ultimate physiologic goal being to increase tissue oxygenation
    • Time Course: changes occur over minutes-weeks
    • Factors Impacting the Degree of Acclimatization
      • Altitude
      • Rate of Ascent
      • Intrinsic Capability of Person to Compensate: related to co-morbid medical conditions, genetic factors, anatomic factors, etc
      • Factors Which Interfere with Compensation: alcohol consumption, medications, temperature, etc
    • Hypoxia-Inducible Transcription factor-1-alpha (HIF-1-a): responsible for activating >350 genes in response to hypoxia
    • Situations in Which There is an Inability to Properly Acclimatize: situations may occur where PIO2 decreases abruptly, not allowing adequate acclimatization
      • Example: rapid cockpit decompression in plane at 8848 m -> PIO2 decreases abruptly to 43.1 mm Hg, which may result in loss of consciousness/death
  • Definition of Adaptation: physiologic changes which take place over generations in populations exposed to chronic high altitude

Cardiovascular

  • Increased Sympathetic Activity
    • Hypertension (see Hypertension, [[Hypertension]])
    • Increased Cardiac Output
    • Increased Venous Tone
    • Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])
  • Decreased Plasma Volume: plasma volume may decrease as much as 12% during the first 24 hrs (due to bicarbonate diuresis, fluid shifts from intravascular space, and inhibition of aldosterone)

Hematologic

  • Increased Hemoglobin (see Polycythemia, [[Polycythemia]]): modest increase in hemoglobin increases oxygen-carrying capacity of blood
    • In first few days at altitude, hemoglobin is increased by plasma volume contraction
    • However, within hours, erythropoietin synthesis is increased in renal cells -> increases red blood cell production over 10-14 days (up to altitudes of 4000m, this increase is sufficient to balance the decrease in SpO2 and restore the oxygen content of arterial blood to sea level values, albeit at a lower pO2)

Neurologic/Neuromuscular

  • Decreased Oxygen Diffusion Distance from Capillaries to Mitochondria: due to decreased diameter of muscle fibers (with atrophy related to a net energy deficit and deconditioning)
  • Improvement in Oxidative Metabolism and Tissue Gas Exchange
  • Increased Blood Flow to Tissues: due to increased angiogenesis and nitric oxide synthesis
    • Due to HIF-1-a associated stimulation of vascular endothelial growth factor (VEGF) synthesis
  • Maintenance of Cerebral Blood Flow and Oxygen Delivery: maintained down to SpO2 of 70-80%

Pulmonary

  • Hypoxic Pulmonary Vasoconstriction/Increased Pulmonary Vascular Resistance (PVR)
    • However, exaggerated pulmonary hypertensive responses are associated with an increased risk of high-altitude pulmonary edema
    • Exercise at altitude may further increase pulmonary artery pressures (sometimes reaching near-systemic levels, especially in patients with a history of high-altitude pulmonary edema)
    • Cold ambient temperatures at high-altitude increase pulmonary artery pressures
  • Hypoxic Ventilatory Response with Resulting Hyperventilation: this is a crucial initial compensatory mechanism, which peaks between 4-7 days at the same altitude
    • Mechanism: hypoxic stimulation of peripheral chemoreceptors (in carotid and aortic bodies), leading to increased minute ventilation (hypoxic ventilatory response)
      • Hypoxic ventilatory response increases linearly with the decrease in SpO2
      • Hypoxic ventilatory response is genetically determined and varies between persons
      • Hypoxic ventilatory response is not related to athletic training
      • Hypoxic ventilatory response is decreased by respiratory depressants (alcohol, sedative medications) and fragmented sleep
      • Hypoxic ventilatory response is increased by respiratory stimulants (progesterone) and sympathomimetics (coca, caffeine)
      • High hypoxic ventilatory response is not necessarily protective against acute mountain sickness: some elite climbers and high-altitude residents (Sherpas, Andeans) have low hypoxic ventilatory responses and perform adequately
      • Low hypoxic ventilatory response is associated with an increased risk of high-altitude pulmonary edema: possibly because it enhances hypoxia-induced pulmonary vasoconstriction (with increased pulmonary pressures)
  • Decreased pCO2 with Respiratory Alkalosis (see Respiratory Alkalosis, [[Respiratory Alkalosis]]): due to hyperventilation
    • Decreased pCO2 in Alveolar Space: decreased dilutional effect of pCO2 in alveolar space
    • Central Medullary Chemoreceptors Respond to Alkalosis in Cerebrospinal Fluid: this mechanism ultimately limits the degree of the hypoxic ventilatory response
      • Peripheral chemoreceptors are less sensitive to changes in pH
  • Hypercapnic Ventilatory Response: decrease in the pCO2 level at which ventilation is stimulated -> this further increases the ventilatory response to high altitude
  • Increased Pulmonary Blood Flow to Underperfused Areas with Improved V/Q Matching: enhances gas exchange
  • Maintained Arterial Oxygen Saturation (SpO2), Despite a Decrease in Arterial pO2
    • Sigmoidal Shape of Oxygen Dissociation Curve: this functions to maintain SpO2 up to an altitude of 3000 m (at approximately 88-89%)
      • However, above 3000 m, small changes in pO2 result in large changes in SpO2
    • Intraerythrocytic Alkalosis
      • Shifts oxygen dissociation curve to left
      • Also stimulates 2,3-DPG synthesis -> shifts oxygen dissociation curve back to the right (back towards normal)

Renal

  • Partial Renal Compensation for Respiratory Alkalosis: occurs within 24-48 hrs of ascent to altitude
    • Renal Bicarbonate Excretion is Enhanced: decreasing the pH toward normal, allowing ventilation to again increase

Diagnosis

Hypobaric Chamber

  • Considered the Gold Standard for Determining the Risk of Hypoxemia at High Altitude

Hypoxia Altitude Simulation Test (HAST) (see Hypoxia Altitude Simulation Test, [[Hypoxia Altitude Simulation Test]])

Background

  • Approximately 741 Million Passengers Traveled on US Commercial Airlines in 2006 (Chest, 2008) [MEDLINE]
  • Approximately 1 Billion Passengers Travel Worldwide Each Year (Chest, 2008) [MEDLINE]
  • Respiratory Complaints are Among the Most Common Necessitating Emergency Calls on Airlines
  • Commercial Aircraft are Pressured to Approximately 8,000 Feet: corresponds to a FIO2 of 15.1%

Indications

  • Screening for Altitude-Associated Hypoxemia in Patients with Cardiopulmonary Disease: HAST aims to identify patients who fall on the steep portion of the hemoglobin dissociation curve and are, therefore, at risk for significant oxygen desaturation at altitude
    • British Thoracic Society Recommendations for Screening Based on Ground SpO2
      • SpO2 >95%: no further testing or supplemental oxygen with air travel is required
      • SpO2 92-95%: HAST is recommended to determine the need for supplemental oxygen with air travel
        • These recommendations recognize that pulse oximeters have large confidence intervals of 2-4%
      • SpO2 <92%: supplemental oxygen is recommended with air travel
    • Aerospace Medical Association Medical Guidelines Task Force Guidelines for Screening Based on Ground pO2
      • Ground pO2 <70 mm Hg: HAST is recommended (Aviat Space Environ Med, 2003)[MEDLINE]

Technique

  • HAST is as Predictive as Measuring Oxygenation in a Hypobaric Chamber (Considered the Gold Standard Test)
  • Testing of SpO2 (or pO2) with the Patient Breathing 15.1% Oxygen (Simulating 8,000 ft = 2,400 m, Pb 565 mm Hg) via a Tight Fitting Mask/Mouth Piece or in a Body Box
    • Concomitant EKG Monitoring
  • Patient Also Wears a Nasal Cannula Beneath the Mask, Allowing Repeat Testing with Supplemental Oxygen

HAST Interpretation

  • pO2 >55 mm Hg During HAST: no supplemental oxygen is required
  • pO2 50-55 mm Hg During HAST: considered borderline -> measurement with activity can then be obtained
  • pO2 <50 m Hg During HAST: testing with supplemental oxygen (usually 2L/min) is performed

Clinical Data

  • Comparative Study of 6MWT and Hypoxia Altitude Simulation Test (HAST) in Patients with Either Interstitial Lung Disease or COPD (Aviat Space Environ Med, 2007) [MEDLINE]
    • Oxygen Desaturation Induced by the 6MWT Correlated with that After HAST (r = 0.52)
  • Study of Algorithm Using Resting/6WMT SpO2 and HAST in COPD Patients (Thorax, 2012) [MEDLINE]
    • Baseline SpO2 <92%: supplemental oxygen is required for air travel
    • Baseline SpO2 92-95%
      • 6MWT SpO2 <84%: supplemental oxygen is required for air travel
      • 6MWT SpO2 ≥84%:
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
    • Baseline SpO2 >95%
      • 6MWT SpO2 <84%
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
      • 6MWT SpO2 ≥84%: no supplemental oxygen is required for air travel

6-Minute Walk Test (6MWT) (see 6-Minute Walk Test, [[6-Minute Walk Test]])

Clinical Data

  • Comparative Study of 6MWT and Hypoxia Altitude Simulation Test (HAST) in Patients with Either Interstitial Lung Disease or COPD (Aviat Space Environ Med, 2007) [MEDLINE]
    • Oxygen Desaturation Induced by the 6MWT Correlated with that After HAST (r = 0.52)
  • Study of Algorithm Using Resting/6WMT SpO2 and HAST in COPD Patients (Thorax, 2012) [MEDLINE]
    • Baseline SpO2 <92%: supplemental oxygen is required for air travel
    • Baseline SpO2 92-95%
      • 6MWT SpO2 <84%: supplemental oxygen is required for air travel
      • 6MWT SpO2 ≥84%:
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
    • Baseline SpO2 >95%
      • 6MWT SpO2 <84%
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
      • 6MWT SpO2 ≥84%: no supplemental oxygen is required for air travel

Risk Stratification by Altitude

High-Altitude (4,921-11,483 ft/1500-3500 m)

  • Incidence of High-Altitude Illness: common with abrupt ascent to >8202 ft (2500m)
  • Physiology
    • Decreased Exercise Performance
    • Hyperventilation
  • Clinical
    • SpO2: minor decrease (usually remains >90%)
    • pO2: 55-75 mm Hg

Very High-Altitude (11,483-18,045 ft/3500-5500 m)

  • Incidence of High-Altitude Illness: most common range for severe high-altitude illness
    • Abrupt Ascent May Be Dangerous: requires a period of acclimatization
  • Clinical
    • SpO2: 75-85%
    • pO2: 40-60 mm Hg
    • Extreme Hypoxia May Occur During Sleep, Exercise, and High-Altitude Illness

Extreme-Altitude (18,045-29,035 ft/5500-8850 m)

  • Incidence of High-Altitude Illness: abrupt ascent almost always precipitates severe high-altitude illness
    • Progressive period of acclimatization is necessary to reach extreme altitudes
    • Above the highest level tolerated for permanent human habitation
  • Physiology
    • Progressive Deterioration of Physiologic Function Eventually Outpaces the Ability to Acclimatize
  • Clinical
    • SpO2: 58-75%
    • pO2: 28-40 mm Hg

Pathologic Clinical Manifestations

Cardiovascular Manifestations

High-Altitude Syncope (see Syncope, [[Syncope]])

  • Epidemiology

Neurologic Manifestations

Acute Mountain Sickness (see Acute Mountain Sickness, [[Acute Mountain Sickness]])

  • Epidemiology: acute mountain sickness and high-altitude cerebral edema (HACE) represent different points along a spectrum of disease
  • Physiology:
  • Clinical:

Chronic Mountain Sickness (Monge’s Disease, Chronic Mountain Polycythemia)

  • Epidemiology

High-Altitude Cerebral Edema (HACE) (see High-Altitude Cerebral Edema, [[High-Altitude Cerebral Edema]])

  • Epidemiology: acute mountain sickness and high-altitude cerebral edema (HACE) represent different points along a spectrum of disease
  • Physiology:
  • Clinical
    • Ataxia (see xxxx, [[xxxx]])

High-Altitude Headache (see Headache, [[Headache]])

  • Epidemiology

Ophthalmologic Manifestations

High-Altitude Retinopathy/Retinal Hemorrhage

  • Epidemiology

Ultraviolet Keratitis (Snow Blindness)

  • Epidemiology

Otolaryngologic Manifestations

High-Altitude Pharyngitis (see Pharyngitis, [[Pharyngitis]])

  • Epidemiology

Pregnancy-Related Manifestations

  • Low Birthweight Infant: increased risk when residing at high-altitude
  • Pre-Eclampsia (see Pre-Eclampsia, Eclampsia, [[Pre-Eclampsia, Eclampsia]]): increased risk when residing at high-altitude
  • Pregnancy-Related Hypertension (see Hypertension, [[Hypertension]]): increased risk when residing at high-altitude

Pulmonary Manifestations

Central Sleep Apnea (CSA)/Periodic Breathing of Altitude (see Central Sleep Apnea, [[Central Sleep Apnea]])

  • Epidemiology: alteration in breathing during non-REM sleep which may be seen at altitudes >2500 m (and is very common at higher altitudes)
    • May occur at altitudes as low at 1400 m, but generally does not disrupt sleep until altitudes >3500 m
  • Physiology: results from changes in neural signaling due to hypoxia (which functions as a respiratory stimulant) and alkalosis (which functions as a respiratory depressant) during sleep
  • Clinical

High-Altitude Bronchitis (see Acute Bronchitis, [[Acute Bronchitis]])

  • Epidemiology

High-Altitude Pulmonary Edema (HAPE) (see High-Altitude Pulmonary Edema, [[High-Altitude Pulmonary Edema]])

  • Epidemiology
  • Physiology
  • Clinical

High-Altitude Pulmonary Hypertension (see High-Altitude Pulmonary Hypertension, [[High-Altitude Pulmonary Hypertension]])

  • Epidemiology

Re-Entry Pulmonary Edema (see Pulmonary Edema, [[Pulmonary Edema]])

  • Epidemiology

Rheumatologic Manifestations

Peripheral Edema (see Peripheral Edema, [[Peripheral Edema]])

  • Epidemiology

Clinical Conditions Which May Be Exacerbated by High-Altitude


Treatment

Supplemental Oxygen (see Oxygen, [[Oxygen]])

  • Clinical Efficacy
    • Study of Algorithm Using Resting/6WMT SpO2 and HAST in COPD Patients (Thorax, 2012) [MEDLINE]
      • Baseline SpO2 <92%: supplemental oxygen is required for air travel
      • Baseline SpO2 92-95%
        • 6MWT SpO2 <84%: supplemental oxygen is required for air travel
        • 6MWT SpO2 ≥84%:
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
      • Baseline SpO2 >95%
        • 6MWT SpO2 <84%
        • HAST SpO2 ≤85%: supplemental oxygen is required for air travel
        • HAST SpO2 >85%: no supplemental oxygen is required for air travel
        • 6MWT SpO2 ≥84%: no supplemental oxygen is required for air travel

References

  • Aerospace Medical Association. Medical guidelines for airline travel, 2nd ed. Aviat Space Environ Med 2003; 74:A1–A19 [MEDLINE]
  • Walking capacity and fitness to fly in patients with chronic respiratory disease. Aviat Space Environ Med 2007;78:789–792 [MEDLINE]
  • Hypoxia altitude simulation test. Chest. 2008 Apr;133(4):1002-5. doi: 10.1378/chest.07-1354 [MEDLINE]
  • The hypoxia altitude simulation test: an increasingly performed test for the evaluation of patients prior to air travel. Chest. 2008 Apr;133(4):839-42. doi: 10.1378/chest.08-0335 [MEDLINE]
  • Flying with respiratory disease. Respiration. 2010;80(2):161-70. doi: 10.1159/000313425. Epub 2010 Apr 16 [MEDLINE]
  • Air travel and chronic obstructive pulmonary disease: a new algorithm for pre-flight evaluation. Thorax. 2012 Nov;67(11):964-9. doi: 10.1136/thoraxjnl-2012-201855. Epub 2012 Jul 5 [MEDLINE]