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PH711: Space medicine - II. Space medicine. Cardiopulmonary problems (heart , lungs).
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Space medicine Cardiopulmonary problems(heart, lungs). • The body has evolved to spend 2/3rds of its time upright within a 1g vertical field. The result of microgravity is to disturb this. The obvious change is in the fluid distribution, with a general shift to the torso and head. • The primary sensors for the cardiovascular system are concentrated in the torso, and passageways to the head. During flight these therefore register a fluid-volume overflow.
Space medicine • Symptoms of the redistribution are very obvious. For example the face becomes puffy, leg girth can be reduced by 30%, but arms are fairly stable. There is a redistribution after return from space (within 24 hours). Source Nicogossian 3rd ed., p 288)
Space medicine • Once in spaceflight the body ‘deduces’ that there is a need to reduce blood volume/mass. This is probably triggered by the change in heart rate and blood pressure as the heart has to do less work to pump blood around the body. • Plasma volume reduces rapidly (within hours) and stabilizes at 12% below normal. It has also been found that there is a reduction in thirst, and hence fluid intake, reducing body water content. Values of 2 to 3.5 % for the reduction in water content have been found.
Space medicine • A consequence of these changes is that the body is ill-equipped for its return to 1 g. This shows up as orthostatic intolerance (problems with standing upright). • The blood mass is also insufficient, and the heart suddenly has to beat faster. • Lying supine (‘horizontally’) reduces these problems, and suddenly standing upright after a long mission can lead to fainting due to hypotension. • Studies in STS flights have focused on loading the body with fluids a few hours before descent. This increases post-flight orthostatic tolerance.
Space medicine • Since 1984, NASA has had a standard procedure where crew drink 32 ounces (2 pints) of water/fruit juice and 8 salt tablets approx. 1 hour before leaving orbit. • If a flight lasts 4 days the result is that upon landing crew show no cardiopulmonary related distress (unlike crew who do not follow this procedure). • However, as mission duration increases the effect of this fluid loading lessens. • At 10 days the effects are close to negligible.
Space medicine • During the first 10 weeks in flight, the rate of heartbeat increases by about 20%, but then falls again (source Nicogossian 2nd ed., p 157). • Pulse pressure falls during a flight. This makes sense, as the heart is not pushing against a hydrostatic pressure as on earth. After return to Earth, both heart beat and pulse fluctuate. • Leg blood flow rates increase during flight. This seems most obviously correlated with the lack of a need to pump against a gravity gradient back to the heart
Space medicine Pre, in-flight and post-flight pulse rate of Skylab astronaut
Space medicine • The heart itself decreases in size by 15% during short flights. • The volume in the heart cavity falls, i.e. less blood pumped per cycle, but an overall increase in the heart beat rate (see previous slide), means no loss of flow rate. • Heart beats are monitored on medical experiments during flights. Slight fluctuations are apparent on short time scales, but after landing the fluctuations disappear.
Space medicine • Lung capacity is also apparently reduced during flight. This may be related to the atmospheric pressure in the crew cabin. 10% reduction in capacity was observed in Skylab crew, but the pressure was at 0.33 atm. • All the above changes are reversed on landing. But recovery time is long. There is a 2 to 3 day period when major changes occur, but there can be longer periods required for full pre-flight behaviour to re-emerge. For long missions the recovery time after say a 100 and 200 day mission is the same. The effects of exercise in flight can affect some improvement in re- adaption. • The above data is from short, medium term studies. Russia has lots of (unreleased) data on the effects of long-term exposure to μg.
Space medicine Changes to muscles • Monitoring these changes during a flight is difficult. X-rays, tissue samples and body fluid sampling are required. • Post-flight investigations have to be immediate. This is to avoid readings changing during recovery. In-flight monitoring is less invasive. It is carried out by measuring various parts of the body and looking for changes. • A better way is complete monitoring of nutrition intake, combined with total sampling of body wastes. • This is time consuming, but was a major exercise on the Skylab missions. The main results are that large losses of calcium, phosphorous and nitrogen occur.
Space medicine • When considering the human body it should be remembered that an average male adult body consists of 40% muscle by volume. Large changes in this volume are thus considerable effects. • All muscle fibres respond to overwork and disuse. • Since the muscles necessary to maintain erect posture are not worked as normal under microgravity, disuse occurs and hence atrophy occurs. • The longer a spaceflight lasts, the greater the atrophy. 2 days is the time for noticeable effects. By 18 to 20 days muscles show significant reduction in muscle fibre mass, diameter, elasticity and strength. • Also muscle tone is also lost (muscle fibres are damaged).
Space medicine • Studies on STS crews show that a 9 day flight causes a 5% loss in muscle volume. • The rate of loss slightly exceeds that of Earth based bed-rest studies (the nearest equivalent to microgravity). • At such rates a 35 day flight could cause a 25% loss of muscle mass (the Russians probably have accurate figures on this). • For the 9 day missions, even 7 days after return there had been no significant recovery of the lost mass. • Biopsy samples reveal structural changes even after just 11 days in flight. The number of capillaries per unit mass decreases significantly. Chemical changes are also observed, with, for example, a decreased capacity for oxidation. This implies that structural protein adaptation commences early (proteins build muscle). • [*NB muscle loss figures don’t include any exercise regime to counter the loss]
Space medicine The force generated by muscles, as well as duration of force generation have both been studied for astronauts. • Reductions in capacity are observed. • The need to prevent this during flight is obvious and the crew must exercise whilst in orbit. They also need to prepare for return to Earth after long missions. • The solutions found include regular exercise. Programs of activity on treadmills are common on Russian space stations. • NASA is developing exercise routines which rely on a variety of approaches. This include bending, stretching, strengthening neck muscles etc by use of elastic restraints against which one must work. • Pingvinsuits (worn several hours a day on Russian missions) can also serve this purpose. The use of suits can also help to load the torso with a pressure which can help redistribute body fluids. • Electrical stimulation of nerves (a form of massage) is used on Russian flights.
Space medicine ISS astronaut using a treadmill. The astronaut is attached to the treadmill via bungee cords. Russian ‘pingvin’ suit (Salyut 3).
Space medicine • Russian studies have also demonstrated that the response of muscles to stimuli is impaired by long missions. 29 cosmonauts who flew between 75 and 130 days each, have been tested on return for response to tickling of the sole. • The normal reflexes are triggered at lower thresholds than pre-flight. The meaning of this is stated to be unclear. • It should be realized that there is no proper model of human body response to microgravity. • One Mir mission included a 450+ day flight by a physician, whose main task was to monitor his own body throughout the mission. • Again, released Russian data on the effects of long term μg are sparse.
Space medicine Changes to bone • The accumulated data indicates that prolonged exposure to microgravity produces increasing changes to bones and their connecting tissue. • Measure calcium loss from the body (normally stored in the bone) is a way to determine the degree of loss. This (calcium loss) may be the most dangerous aspect of space flight for humans. • After return to earth, this loss can take a long time to be replaced. 90 days after return there can still be significant loss compared to pre-flight (Skylab data).
Space medicine • Four Salyut-7 cosmonauts were studied after missions, two after 5 month flights, and two after 7 month flights. All 4 had lost vertebral bone (-6.1%, -0.3%, -2.3% and -10.8% respectively). • Muscle mass in the posterior-vertebral region was also lost. • More bone was lost from the posterior-vertebral region than from the vertebrae as a whole (-8.1%, -3.7%, -7.5%, -11.9% respectively). • Observation: cosmonaut #2 was least susceptible. Why?
Space medicine • Using absorption techniques, the mineral content of bone can be determined. • Some changes were found for cosmonauts on 131 to 312 day flights. This was in spite of exercising during flight for 2 hours per day. • 5 to 10% mineral content decreases were observed in isolated parts of the body, but other cosmonauts had no loss (person specific). • During flights, measurement has focussed on dietary and waste measurements. • In Skylab, waste produced during flight was sampled and stored. The intake from the diet was considered, and a balance found. Mineral loss due to sweat etc was not taken into account.
Space medicine • The figure below shows the changes in calcium loss during the Skylab-4 mission. (Nicogossian, 3rd ed., p329).
Space medicine • The Skylab data show a plateau in loss via urine, but increasing loss via solid waste. • Over 90 days 0.8% of whole body calcium was lost (10g out of normal 1250g in body). • Over a 1 year mission the extrapolation suggests a 25% loss! • The data for the Russian flights of 1 year duration are not available, but reports are that exercise reduced calcium loss. • It is supposed that loss occurs in load bearing structures, e.g. leg and heel regions. US studies failed to support this theory, suggesting that loss occurs throughout the body. • There is no rapid return to pre-flight levels after return to Earth (bone growth is slow). • This is a major risk for human spaceflight as irreversible skeletal damage may occur – referred to as ‘spaceflight osteopenia’.
Space medicine • Female astronauts may be particularly susceptible to risk here. • Later in life women undergo natural hormonal changes which can affect the mineral content of the bone (osteoperosis). • If they have suffered damage earlier in life this natural situation may be exacerbated into a serious health hazard. • There are few data available - no long duration female flights have occurred. The Russians have proposed a long (300 day) mission in the near future for a female cosmonaut. The Russians called for female volunteers to spend 6 months in bed to study these effects on Earth.
Space medicine • As a reverse of this problem, medical researchers on Earth are very interested in mineral loss in astronauts (particularly women), as well as their subsequent re-adaptation on earth. • This is as a means of finding out more about the natural losses that occur to woman. Measures to reverse these losses would be a major scientific breakthrough in women's medicine. • For example, why was cosmonaut #2 less predisposed to suffer calcium loss? Genetics, diet, exercise, blood type???
Space medicine • During flights, urine analysis indicates significant losses of phosphorous, hydroxyproline (indicating loss of material from the collagen matrix within bones), nitrogen (muscle atrophy) and various acids. • In 2004 a study by American researchers of 14 US and Russian astronauts who had each spent 4 to 6 months on the ISS found that between 1.6 and 2.7% of bone was lost per month in space. In addition, hip-bone strength decreased by 2.5% per month in space. • They predicted problems for crews returning to Earth after long duration missions to Mars (estimated flight time 6-12 months).
Space medicine Solution: artificial gravity? Possibly. But problems exist. To get 1g – the rotating part of the spacecraft would have to be 200 metres in length. This is to reduce the effects of coriolis (and centrifugal) forces. Totally unknown what the effect of long-term ‘spinning’ on the human body is.
Space medicine Radiation • A major concern, especially for long duration flights to mars, the asteroid belt is the effects of ionising radiation on an astronaut. • The magnetic field around the Earth, plus the Earth's atmosphere normally shield humans from the worst of stellar radiation. Venturing into space can remove this shielding. • Low Earth Orbit is the safest of any orbit, as it is still shielded by much of the magnetic field effect. However, there are holes in the shielding (South Atlantic Anomaly-SAA) so orbits have to be plotted correctly to minimize doses.
Space medicine • EVA's are clearly more hazardous (particularly if they coincide with orbits through the SAA). • Further, normal calculations of steady state exposure in orbit are exceeded by single events (e.g. solar flares) which can deliver a (relatively) large whole body dose in a short time. • A question is how much shielding do you provide vs. the probability of a large flare event? Shielding is heavy and thus expensive.
Space medicine • The SI unit of absorbed dose is the Gray, and measures the energy absorbed per unit mass (1 gray = 1 Joule absorbed per kilogram). • The old unit was the rad, 1 rad = 0.01 Gy. It is still widely used. • Effects of any particular radiation clearly depend on the target material (i.e., how well it absorbs energy from ionising radiation/high energy particles – its interaction cross-section). • For humans it is convenient to consider the absorbing material as water (although this is an oversimplification and many complicated radiation absorption models exist).
Space medicine • A complication for life forms is that the amount of energy deposited in a small volume causes biological damage (as opposed to just localised heating for ‘inert’ materials). • Large energy loss per unit length (i.e. high z particle or target), is more hazardous than low dE/dx. • This is measured by Linear Energy Transfer (LET). • Q: Is a high flux low LET dose better/worse than a low flux high LET dose ? (i.e. is a dose of a large amount of low energy radiation worse than a small amount of high energy radiation?).
Space medicine • This is answered by considering dose equivalents (DE). • This is the flux of low LET radiation which produces the same biological effect as a high LET dose. • The observed high LET dose is converted to a DE by a ‘wr’factor (‘radiation weighting factor’, previously called the Q factor). • The unit of DE is the Sievert, i.e. absorbed dose in Gys multiplied by wr. • The Sievert replaces the rem (old unit), where 1 Sv = 100 rem.
Space medicine • In the US space program two types of monitors are used to measure doses. • Passive monitors are sealed units (e.g. film badges) and are analyzed after recovery. • Active monitors give real time readout (or integrate over short periods). • Most active detectors measure ionization (e.g. ion chambers, Geiger counters). • Usually a range of sensitivities are required so monitors simultaneously run for the ranges: 0 to 2 mGy, 0 to 1 Gy and 0 to 6 Gy.
Space medicine • Measured fluxes: • 0.1 mGy/day on Gemini 4, • 1 mGy/day on Skylab, • 0.06 mGy/day on the first 51 STS flights. • Mission doses ranged from 2 to 11.4 mGy for Apollo (with an average of 0.4 mGy per day). • For Skylab, exposure increased with mission duration, with the maximum of 77.4 mGy for Skylab 4. • Normalization of dose between missions is difficult as the monitors are inside the craft; the degree of shielding often being unknown. • Solar events such as Solar Particle Events (SPE) which sometimes accompany Solar flares, can increase the dose rates enormously, such that if there were no shielding an astronaut could receive 1 Sv in a few hours.
Space medicine • X and gamma rays set electrons in motion in the target and ionise atoms, so are similar in effect to low energy electrons. • Protons or heavier particles can cause nuclear damage. • Low LET radiation damages DNA, breaking single and occasionally double strands. Single strand DNA breaks are naturally repaired, double are not. • High LET radiation causes more double breaks, and is thus more dangerous. This is an example of relative biological effectiveness (RBE). • Such damage results in decreased cell survival, increased cell mutation, increased chromosome aberrations, malignant transformation and cancer.
Space medicine • After recovery from a low LET exposure, ability to survive a second such exposure is not impaired. The risk is therefore linear for multiple missions. • Protons have a different energy loss profile. There is a low LET at a constant rate, and then the particle reaches its range and stops, depositing a large amount of radiation. • Studies have shown that such a profile is not significantly worse than that for electrons etc. for humans.
Space medicine • If radiation exposure occurs, effects show up on two time scales, immediate and long term. • The first table below (source Nicogossian 3rd ed., page 175) show short term effects from acute whole body radiation. • Note that a typical person receives ~3 mSv/yr from general background radiation. • Radiation workers (hospital workers, firemen etc) are limited to 15 mSv/yr (UK) or 50 mSv/yr (US). • Based on a 12 month round trip to Mars (and using Apollo exposure data) an astronaut would experience ~4 – 80 Sv of radiation (depending on wr). A solar event during the trip could significantly increase this!
Space medicine • It can be seen that a short exposure to approx. 3.5 Sv results in 50% of population dying within 30 days. This is the LD50 30 day dose. • The long term effects of exposure are tumours, mutations, cataracts etc. Tumours depend on irradiated tissue, age, sex, genetic background. • Calculation of the long term effects of radiation is poor. It seems that every decade there is a revision of the observations on the Hiroshima and Nagasaki populations. • The full effects of the Chernobyl disaster are also not completely known – but increased instances of leukaemia in the local population are definite.
Space medicine The table below gives current NASA exposure limits for STS crews (source Nicogossian, 3rd ed., page 185). Note that for single events (SPEs) and missions away from LEO it will be impossible to keep to these limits with present spacecraft/suit design. However, the ALARA principle has to be adopted: As Low As Reasonably Possible.
Space medicine Gender differences? • There are physiological differences between men and women which may effect their health differently on a long duration spaceflight. • Main problem: not many female astronauts/cosmonauts. No long duration flights with female crew, so very little data!
Space medicine Stress. • Space missions (short or long) are inherently stressful events. In men stress is known to affect hormone levels. This is in itself not harmful during missions, and is reversible on landing, but can lead to depressive moods and mood swings. • In women, stress is also known to alter hormone levels. In particular it can suppress oestrogen production. • Oestrogen is necessary for healthy bones, and suppression results in calcium loss. This will compound calcium loss which is already occurring due to weightlessness. This is a serious health hazard. • HRT (Hormone Replacement Therapy) may be a way forward – used for post-menopausal women suffering from osteoperosis. Or women who suffer premature menopause.
Space medicine Pregnancy • Soft tissue is particularly susceptible to acceleration induced damage. Thus launch/landing during pregnancy will be hazardous for a foetus and mother. • It is also known that stress (and related hormonal changes) can have an adverse effect on the foetus. • Radiation damage is also worse in soft tissue and developing cells. A foetus is thus particularly at risk. • It is therefore usually concluded that space is not (currently) an acceptable environment for pregnant women. Again, no data.
Space medicine Weightlessness: Muscle and calcium loss. • Female musculature is different from male. When muscle atrophy occurs will there be any different effects ? Does this question have any significance ? Again, no data. • Calcium loss is a much more serious issue. Fragile bones are a health hazard, they can snap. • So for all astronauts this is a risk area. For women it is compounded by the stress related risk as well (if this is serious). • Further, having returned to Earth, the lost calcium is returned slowly, and not necessarily completely. • Women undergo natural calcium loss after the menopause. If they have already suffered an extended period of loss, what will happen to them in later life ? This risk is not quantified, but it cannot be assumed that it can be neglected either
Space medicine Radiation. • Radiation can cause scar tissue/damaged sites in the ovaries etc which can cause menstruation problems. • Since women have soft tissue areas (breasts, ovaries etc) lacking in men they can have increased risks of cancers. Reproductive tissue areas and soft tissue has a higher radiation weighting factor, wr. • By contrast, they will not suffer testicular cancer. • The relative risks of male/female susceptibility to cancer induced by radiation have not been fully investigated as regards the space environment.
Space medicine Psychological considerations • This lecture has just touched on some of the physical problems of spaceflight. • What are the mental effects of a long duration spaceflight? Mir crews were well trained military personnel who knew that if anything went wrong a rescue Soyuz could be sent to rescue them (similarly ISS). • A flight to Mars is a different question – there would, in all likelihood, be no rescue. What effect would that have on the mental health of the crew? • Over-wintering in Antarctica is probably the closest people normally come to such a situation. Total isolation for ~9 months. • For a mission to Mars how do you determine the crew makeup? All military, all scientific, all men, all women?
