Living and Working on the Moon – some Physiology Issues
or
The Highs and Lows of Oxygen
Johnny Conkin, Ph.D.
[with help from Jeff Jones, Richard Scheuring,
Mike Gernhardt, Ramachandra Srinivasan,
James Wessel, III, and James M. Waligora]
Universities Space Research Association
March 20, 2008
we will stay longer and do more EVAs
topics
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CEV (Orion), LSAM, and habitat atmospheres
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mild hypoxia - problem with Equivalent Air Altitude concept
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unintended consequences - haemoconcentration
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yo-yo ppO2 exposures and superoxide radicals
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integrated physiological response
spacecraft atmosphere trade study - 2006
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Underlying Assumptions:
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Efficient and frequent EVAs will drive exploration program.
Low pressure suit is always preferred to high pressure suit.
There is operational value to a short in-suit prebreathe.
Vehicle atmosphere may not prevent risk of DCS during EVA.
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Shuttle and ISS atmospheres are examples.
Dedicated hyperbaric treatment capability may not be present.
Atmosphere Design Considerations:
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No significant risk of fire – bad experience with 100% O2.
Limit hypoxia – you need O2 with every breath.
Prevent DCS and VGE.
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Better to prevent than treat DCS, or to constantly embolize the lung.
Optimize atmosphere to allow safe and efficient EVAs.
future spacecraft atmospheres
Actual Altitude
m
ft
Equivalent Air
Altitude
m
ft
77
4,877 16,000
1,829 6,000
128
86
4,816 15,800
1,158 3,800
30.0
107
68
5,029 16,500
2,438 8,000
393
32.0
111
71
5,182 17,000
2,286 7,500
7.8
403
34.0
121
80
5,029 16,500
1,524 5,000
7.4
383
30.0
101
63
5,364 17,600
2,895 9,500
PB
psia mmHg
FIO2
(%)
PIO2
mmHg
normal
8.0
414
32.0
117
best case
8.2
424
34.0
worse case
7.8
403
normal
7.6
best case
worse case
Environment
PAO2
mmHg
CEV + LSAM
HABITAT
PIO2 is inspired O2 partial pressure, computed as (PB mmHg – 47) * FIO2 (as decimal fraction).
PAO2 is computed acute alveolar oxygen partial pressure from alveolar oxygen equation.
equivalent air altitude model - ascent on enriched O2
ambient oxygen fraction
0.45
150
0.40
130
0.35
110
0.30
0.25
EAA model
80
0.20
0.15
50
0.10
0.05
250
350 450 550 650 750
ambient pressure (mmHg)
850
FIO2 = PIO2 / (PB – 47)
the issue
PIO2 = (PB – 47) * FIO2
therefore it follows
(PB(1) – 47) * FIO2(1) = (PB(2) – 47) * FIO2(2)
but
body response 1 ≠ body response 2
certainly when PIO2 is hypoxic
acute mountain sickness
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Signs and symptoms include headache, nausea,
dizziness, fatigue, vomiting and sleeplessness
following a recent gain in altitude with at least
several hours at the new altitude in a hypoxic
environment; likened to a bad hangover.
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Anyone here had AMS – not just a hangover?
“typical” response to hypobaric
hypoxic exposure
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Ascent causes a decrease in PaO2 sensed by the
peripheral and central chemoreceptors, leading to
increased minute ventilation rate (VE) – but some
show little change in VE.
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Hyperventilation in response to hypoxia increases
PAO2 and subsequently decreases PACO2 and leads
to a transient alkalosis.
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There is also a hypoxia-induced diuresis as the
kidney attempts to establish normal pH with the
excretion of bicarbonate – but some show little
change in urine output.
the spectrum of hypoxia
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Sudden ascent to high altitude would kill due to
acute hypoxia while a gradual ascent could
result in AMS or no symptoms at all.
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Symptoms of AMS take hours to days to develop
– seriously disturbed sleep: frequent arousals,
periodic breathing, incessant dreaming.
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Severe and prolonged hypoxic exposure may
lead to High Altitude Pulmonary Edema, High
Altitude Cerebral Edema, and even death.
acute hypobaric hypoxia video
incidence of mild AMS
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The incidence of AMS is highly variable.
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Roach (1998) reports that 25% of people are affected
by a quick ascent to 2,000 m (6,600 ft).
Montgomery (1989) shows 25% incidence of three or
more symptoms at 2,000 m and that half with these
symptoms took medication for relief of symptoms.
Houston (1982) starts his list of AMS symptoms at
altitudes above 2,100 m (7,000 ft).
Muhm (2007) reports 11% AMS in large sample
during 20 hrs at 2,438 m (8,000 ft).
How do results from these actual altitudes
translate to Equivalent Air Altitude?
Lake Louise AMS Scoring System
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Based on this 1991 committee’s recommendations:
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A diagnosis of AMS is based on a recent gain in altitude, at
least several hours (>2) at the new altitude, and the presence
of headache and at least one of the following symptoms:
gastrointestinal upset, fatigue or weakness, dizziness or
lightheadedness and difficulty sleeping.
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A score of three points or greater on the AMS Self-Report
Questionnaire alone or in combination with the clinical
assessment score is diagnostic of AMS.
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Several signs and symptoms of AMS are shared with
motion sickness – confounding a diagnosis of each!
Self Report
Questionnaire
Each question asked and
the sum is calculated as
the AMS self report score.
1. Headache
2. Gastrointestinal
Symptoms
3. Fatigue and/or
Weakness
4. Dizziness /
lightheadedness
5. Difficulty sleeping
0
No headache
1
Mild Headache
2
Moderate Headache
3
Severe Headache, incapacitating
0
No gastrointestinal symptoms
1
Poor appetite or nausea
2
Moderate nausea or vomiting
3
Severe nausea & vomiting, incapacitating
0
Not tired or weak
1
Mild fatigue/weakness
2
Moderate fatigue/weakness
3
Severe fatigue / weakness, incapacitating
0
Not Dizzy
1
Mild dizziness
2
Moderate dizziness
3
Severe dizziness, incapacitating
0
Slept as well as usual
1
Did not sleep as well as usual
2
Woke many times, poor night's sleep
3
Could not sleep at all
Clinical Assessment
The interviewers ratings of
three signs is added to the
self-report score.
6. Change in Mental
Status
7. Ataxia (heel to
toe walking)
8. Peripheral Edema
0
No Change in Mental Status
1
Lethargy / lassitude
2
Disoriented/confused
3
Stupor / semiconsciousness
4
Coma
0
No Ataxia
1
Maneuvers to maintain balance
2
Steps off line
3
Falls down
4
Can't stand
0
No peripheral edema
1
Peripheral edema at one location
2
Edema at two or more locations
a debate is underway
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Despite over a century of research there is
still vigorous debate on the cause of AMS.
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Certainly the brain is the target organ of and
first responder to O2 deprivation.
Paul Bert (1833-1886)
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A French Physiologist considered the
founder of Aerospace Medicine.
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Demonstrated that the symptoms of AMS
are prevented or relieved by breathing O2
– enriched air.
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So “proved” that it was the decrease in
partial pressure of O2 that caused AMS.
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The doctrine that low partial pressure of O2
alone is the cause for AMS has dominated
our thoughts.
observations through the years
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Rahn and Fenn (1956) disproved the simple notion of
Equivalent Air Altitude, and conclude, “It is evidently not
enough to equate the inspired O2 tensions …”
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Since 1980s researchers have questioned the
conventional wisdom that the symptoms of AMS are
solely due to low O2 partial pressure.
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Accumulated anecdotal evidence shows descent is more
effective for relief of AMS than enriched O2 alone.
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Savourey (2003) speaks of the “specific response to
hypobaric hypoxia”.
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So the door is open to investigate an independent PB
effect on AMS.
Tucker, 1983
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Starts his experiments with subjects living at 1,524 m (5,000 ft –
Colorado State University).
Takes them to 15,000 ft on air and site pressure on 14% O2.
Normobaric,
PB = 760
mmHg
Normoxic, PAO2 =
103 mmHg
Hypoxic, PAO2<103
mmHg
Altitude 1520
PAO2 = 77
No AMS symptoms
Altitude 1520 m
PAO2 = 47
Mean AMS Score: 3.2
Hypobaric
PB<760 mmHg
Environmental Symptoms Questionnaire
Altitude 4570 m
PB = 430 mmHg
PAO2 = 45
Mean AMS Score: 5.7
with denitrogenation
and 7.3 without !
Roach and Loeppky, 1996
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Also starts experiment at 5,000 ft – University of New
Mexico.
They confirm the PB effect on the incidence of AMS.
Normoxic, PAO2 =
103 mmHg
Hypoxic, PAO2<103
mmHg
Normobaric,
PB = 760
mmHg
Altitude 1520 m
PAO2 = 76
No AMS symptoms
Altitude 1520 m
PAO2 = 47
Mean AMS Score: 2.0
Hypobaric
PB<760
mmHg
Altitude 4570 m
PAO2 = 74
Mean AMS score: 0.4
Altitude 4570 m
PAO2 = 46
Mean AMS Score: 3.7
Lake Louise scoring system
the PB effect!
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The pressure effect seems real, so to
understand the total hypoxic stress means
you have to understand the interaction
between hypoxic PIO2 and PB.
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A variety of explanations have been
proposed for a PB effect on AMS.
HH versus NH
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Decreased gas density in HH
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work of breathing.
insensible water loss.
Transient N2 gradient out of tissues in HH
and into tissues in NH condition
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N2 gradient in HH for the same PIO2
between HH and NH.
z Takes
longer in HH to come to new N2
equilibrium.
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Potential for VGE in HH
mechanics of breathing
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Alveolar ventilation (VA) is influenced by
PB:
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is ∝ to 1/√ gas density
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of breathing is ∝ to relative density * VE3
z Diffusivity
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of a gas is ∝ 1 / gas density
These effects combined with differences in
transient N2 kinetics do make NH and HH
different.
consider work of breathing
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A decrease in VCO2 and VO2 decreases RER in
HH relative to NH.
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Loeppky (1997) shows:
test
PIO2
VE
VA
VCO2
VO2
mmHg
l / min
l / min
ml / min
ml / min
NH
80
13.6
9.6
309
335
0.92
HH
80
10.3
7.4
226
263
0.86
RER
(15,000 ft)
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A decrease in RER decreases PAO2 and PACO2
in HH relative to NH.
consider the role of N2
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N2 concentration gradient is into the body in NH and out
of the body in HH.
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A change in N2 concentration gradient changes the
equilibrium FEN2 / FIN2 ratio for a given RQ.
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As N2 moves from the lung to the tissues in NH there is a
slight decrease in lung gas volume leading to slightly
higher PAO2 and PACO2 and a smaller FEN2 / FIN2 ratio.
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As N2 moves from the tissues to the lung in HH there is
a slight increase in lung gas volume leading to slightly
lower PAO2 and PACO2 and a larger FEN2 / FIN2 ratio.
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Less work of breathing and N2 movement out of tissues
drives PAO2 and PACO2 lower in HH relative to NH.
Savourey’s and Loeppky’s summary with
PIO2 of 81 mmHg
Test
PIO2
(mmHg)
PETO2 PETCO2
(mmHg)
(mmHg)
NH
81
higher higher
HH
81
lower
lower
Savourey’s 40 minute test in 15 subjects with
PIO2 of 81 mmHg
Test
NH
PIO2
PaO2
PaCO2
(mmHg)
(mmHg)
(mmHg)
81
51.7
37.9
81
47.8
34.8
(12% O2)
HH
(15,000 ft)
Arterial blood gases obtained at end of 40 min
test.
consider the brain
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For the same hypoxic PIO2 at different PBs:
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PCSFO2 and PCSFCO2 is transiently higher in the NH
relative to HH.
VE should therefore be higher, and it is.
Cerebral blood flow may be lower in HH relative to NH.
Presentation of AMS should be different, and it is.
One only needs to measure PCSFO2 and pH
through time given identical hypoxic PIO2 at two
different PBs to test the basic hypothesis.
accounting for the PB effect on AMS
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A precise model does not yet exist.
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A new iso-hypoxic model would be a refinement
of the current Equivalent Air Altitude model,
which empirical data suggests needs to be
refined.
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You need to increase both PIO2 and PICO2 a bit
in the breathing mix at altitude to achieve the
same hypoxic condition tested at sea level.
three hypoxic isopleths
0.350
iso-hypoxic
model
ambient oxygen fraction
0.325
0.300
0.275
90
80
0.250
110
0.225
0.200
100
0.175
0.150
0.125
0.100
250
____
FIO2 = PIO2 / (PB – 47)
350 450 550 650 750
ambient pressure (mmHg)
850
----- FIO2 = √(PB – 47) * 100 / (dose + 0.02) * (PB – 47)2
NASA atmosphere experience
1.0
ambient oxygen fraction
0.9
0.8
211-Apollo
NASA
148-Skylab
0.7
0.6
0.5
117-CEV
111-habitat
0.4
0.3
0.2
0.1
200
80
?
127-Shuttle
Loeppky
300 400 500 600 700
ambient pressure (mmHg)
800
So…..
Are astronauts at risk for AMS? -- yes about
25% worse case probability early in mission
with 0% once acclimatization occurs.
At greater risk than the 6,000 ft (CEV/LSAM)
and 7,500 ft (habitat) Equivalent Air Altitude
suggests.
Develop a plan to mitigate the risk even if risk
is unclear.
to reiterate -- performance
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We are dealing with performance issues
and mission success, not life and death,
with the AMS anticipated in the CEV.
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We want to maximize performance and
minimize any medical issues that impact
mission success – our job.
prevention and treatment of AMS
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Preadaptation
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Preselection
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The best predictor of AMS is history of prior episodes.
Mild AMS is prevented / treated by:
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Halting or slowing ascent – phased hypoxic exposure
Denitrogenation
Acclimatization
Acetazolamide (125-250 mg BID)
O2 therapy via mask or canula
other considerations
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Does μG modify the likelihood or character of
AMS?
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Redistribution of lung fluid – 25% increase in CapBV
Increased interstitial edema – puffy face response
Increased incidence of HAPE?
Potential negative synergy on combining mild
hypoxia and adaptation to μG – increase in
hematocrit leads to increased blood viscosity.
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Six reports suggest this may not be a significant
concern – keep hematocrit below 55%
Dr. Srinivasan is updating the Skylab Erythropoiesis
Model.
EP concentration (mU/ml or um/l)
erythropoietin -- PIO2 and time
30
28
26
24
22
20
18
16
14
12
10
0
A
B
C
D
A = 2805 meters (PIO2 = 103 mmHg)
B = 2454 meters (PIO2 = 108 mmHg)
C = 2085 meters (PIO2 = 114 mmHg)
D = 1780 meters (PIO2 = 119 mmHg)
5
10
15
TIME (HRS)
20
25
Ge Ri-Li, et al. Determinants of erythropoietin release in response to short-term
hypobaric hypoxia. J Appl Physiol 92: 2361-67, 2001.
Basu M, et al. Erythropoietin levels in lowlanders and high-altitude natives at 3,450 m.
Aviat Space Environ Med 78:963-67, 2007.
optimum HCT for O2 transport
yo-yo ppO2 exposures
Repetitive exposure to mild hypoxic (habitat) and mild
hyperoxic (suit) environments may have biochemical
consequences – no one does this type of repetitive long-term
operation.
Living at a habitat PIO2 of 111 mmHg for 40 hrs with EVA
exposures to 175 mmHg for 8 hrs may have unexpected
cumulative effects?
This is like living at sea level in 15% O2 for 40 hrs and then 25%
O2 for 8 hrs – over and over and over again.
The up-and-down regulation of antioxidant enzyme systems
(superoxide dismutase and catalase) over many months may
exhaust the ability to manage reactive O2 species.
additional information?
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A copy of this PowerPoint presentation.
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Conkin J. Risk assessment of acute mountain sickness
in the crew exploration vehicle. NASA/TP-2008-214759,
Johnson Space Center, Houston, Tx, January 2008.
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Scheuring RA, Conkin J, Jones JA, Gernhardt ML. Risk
assessment of physiological effects of atmospheric
composition and pressure in Constellation vehicles.
Acta Astronautica (in press).
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Conkin J, Wessel JH, III. Critique of the equivalent air
altitude model. Aviat Space Environ Med (in review).
thank you for your time