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
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%
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
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
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]])
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]
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]
