THE EFFECTS OF ALTITUDE ON HUMAN PHYSIOLOGY
 
 
 
         Changes in altitude have a profound effect on the human body. The body
 attempts to maintain a state of homeostasis or balance to ensure the optimal
 operating environment for its complex chemical systems. Any change from this
 homeostasis is a change away from the optimal operating environment. The body
 attempts to correct this imbalance. One such imbalance is the effect of
 increasing altitude on the body's ability to provide adequate oxygen to be
 utilized in cellular respiration. With an increase in elevation, a typical
 occurrence when climbing mountains, the body is forced to respond in various
 ways to the changes in external
 environment. Foremost of these changes is the diminished ability to obtain
 oxygen from the atmosphere. If the adaptive responses to this stressor are
 inadequate the performance of body systems may decline dramatically. If
 prolonged the results can be serious or even fatal. In looking at the effect
 of altitude on body functioning we first must understand what occurs in the
 external environment at higher elevations and then observe the important
 changes that occur in the internal environment of the body in response.
 
 HIGH ALTITUDE
         In discussing altitude change and its effect on the body mountaineers
 generally define altitude according to the scale of high (8,000 - 12,000
 feet), very high (12,000 - 18,000 feet), and extremely high (18,000+ feet),
 (Hubble, 1995). A common misperception of the change in external environment
 with increased altitude is that there is decreased oxygen. This is not
 correct as the concentration of oxygen at sea level is about 21% and stays
 relatively unchanged until over 50,000 feet (Johnson, 1988).
         What is really happening is that the atmospheric pressure is decreasing and
 subsequently the amount of oxygen available in a single breath of air is
 significantly less. At sea level the barometric pressure averages 760 mmHg
 while at 12,000 feet it is only 483 mmHg. This decrease in total atmospheric
 pressure means that there are 40% fewer oxygen molecules per breath at this
 altitude compared to sea level (Princeton, 1995).
 
 HUMAN RESPIRATORY SYSTEM
         The human respiratory system is responsible for bringing oxygen into the
 body and transferring it to the cells where it can be utilized for cellular
 activities. It also removes carbon dioxide from the body. The respiratory
 system draws air initially either through the mouth or nasal passages. Both
 of these passages join behind the hard palate to form the pharynx. At the
 base of the pharynx are two openings. One, the esophagus, leads to the
 digestive system while the other, the glottis, leads to the lungs. The
 epiglottis covers the glottis when swallowing so that food does not enter the
 lungs. When the epiglottis is not covering the opening to the lungs air may
 pass freely into and out of the trachea.
         The trachea sometimes called the "windpipe" branches into two bronchi which
 in turn lead to a lung. Once in the lung the bronchi branch many times into
 smaller bronchioles which eventually terminate in small sacs called alveoli.
 It is in the alveoli that the actual transfer of oxygen to the blood takes
 place.
         The alveoli are shaped like inflated sacs and exchange gas through a
 membrane. The passage of oxygen into the blood and carbon dioxide out of the
 blood is dependent on three major factors: 1) the partial pressure of the
 gases, 2) the area of the pulmonary surface, and 3) the thickness of the
 membrane (Gerking, 1969). The membranes in the alveoli provide a large
 surface area for the free exchange of gases. The typical thickness of the
 pulmonary membrane is less than the thickness of a red blood cell. The
 pulmonary surface and the thickness of the alveolar membranes are not
 directly affected by a change in altitude. The partial pressure of oxygen,
 however, is directly related to altitude and affects gas transfer in the
 alveoli.
 
 GAS TRANSFER
         To understand gas transfer it is important to first understand something
 about the
 behavior of gases. Each gas in our atmosphere exerts its own pressure and
 acts independently of the others. Hence the term partial pressure refers to
 the contribution of each gas to the entire pressure of the atmosphere. The
 average pressure of the atmosphere at sea level is approximately 760 mmHg.
 This means that the pressure is great enough to support a column of mercury
 (Hg) 760 mm high. To figure the partial pressure of oxygen you start with the
 percentage of oxygen present in the atmosphere which is about 20%. Thus
 oxygen will constitute 20% of the total atmospheric pressure at any given
 level. At sea level the total atmospheric pressure is 760 mmHg so the partial
 pressure of O2 would be approximately 152 mmHg.
 
                                 760 mmHg x 0.20 = 152 mmHg
 
 A similar computation can be made for CO2 if we know that the concentration
 is approximately 4%. The partial pressure of CO2 would then be about 0.304
 mmHg at sea level.
         Gas transfer at the alveoli follows the rule of simple diffusion. Diffusion
 is movement of molecules along a concentration gradient from an area of high
 concentration to an area of lower concentration. Diffusion is the result of
 collisions between molecules. In areas of higher concentration there are more
 collisions. The net effect of this greater number of collisions is a movement
 toward an area of lower concentration. In Table 1 it is apparent that the
 concentration gradient favors the diffusion of oxygen into and carbon dioxide
 out of the blood (Gerking, 1969). Table 2 shows the decrease in partial
 pressure of oxygen at increasing altitudes (Guyton, 1979).
 
 
 Table 1
                 ATMOSPHERIC AIR         ALVEOLUS                VENOUS BLOOD
 OXYGEN            152 mmHg (20%)         104 mmHg (13.6%)       40 mmHg
 CARBON DIOXIDE  0.304 mmHg (0.04%)      40 mmHg (5.3%)  45 mmHg
 
 
 Table 2
 ALTITUDE (ft.)  BAROMETRIC PRESSURE (mmHg)      Po2 IN AIR  (mmHg)      Po2 IN ALVEOLI
 (mmHg)  ARTERIAL OXYGEN SATURATION (%)
  0                    760               159*    104             97
  10,000         523             110             67              90
  20,000         349             73              40              70
  30,000         226             47              21              20
  40,000         141             29              8               5
  50,000         87              18              1               1
 
         *this value differs from table 1 because the author used the value for the
 concentration of O2 as 21%.
 The author of table 1 choose to use the value as 20%.
 
 
 CELLULAR RESPIRATION
         In a normal, non-stressed state, the respiratory system transports oxygen
 from the lungs to the cells of the body where it is used in the process of
 cellular respiration. Under normal conditions this transport of oxygen is
 sufficient for the needs of cellular respiration. Cellular respiration
 converts the energy in chemical bonds into energy that can be used to power
 body processes. Glucose is the molecule most often used to fuel this process
 although the body is capable of using other organic molecules for energy.
         The transfer of oxygen to the body tissues is often called internal
 respiration (Grollman, 1978). The process of cellular respiration is a
 complex series of chemical steps that ultimately allow for the breakdown of
 glucose into usable energy in the form of ATP (adenosine triphosphate). The
 three main steps in the process are: 1) glycolysis, 2) Krebs cycle, and 3)
 electron transport system. Oxygen is required for these processes to function
 at an efficient level. Without the presence of oxygen the pathway for energy
 production must proceed anaerobically. Anaerobic respiration sometimes called
 lactic acid fermentation produces significantly less ATP (2 instead of 36/38)
 and due to this great inefficiency will quickly exhaust the available supply
 of glucose. Thus the anaerobic pathway is not a permanent solution for the
 provision of energy to the body in the absence of sufficient oxygen.
         The supply of oxygen to the tissues is dependent on: 1) the efficiency with
 which blood is oxygenated in the lungs, 2) the efficiency of the blood in
 delivering oxygen to the tissues, 3) the efficiency of the respiratory
 enzymes within the cells to transfer hydrogen to molecular oxygen (Grollman,
 1978). A deficiency in any of these areas can result in the body cells not
 having an adequate supply of oxygen. It is this inadequate supply of oxygen
 that results in difficulties for the body at higher elevations.
 
 ANOXIA
         A lack of sufficient oxygen in the cells is called anoxia. Sometimes the
 term hypoxia, meaning less oxygen, is used to indicate an oxygen debt. While
 anoxia literally means "no oxygen" it is often used interchangeably with
 hypoxia. There are different types of anoxia based on the cause of the oxygen
 deficiency. Anoxic anoxia refers to defective oxygenation of the blood in the
 lungs. This is the type of oxygen deficiency that is of concern when
 ascending to greater altitudes with a subsequent decreased partial pressure
 of O2. Other types of oxygen deficiencies include: anemic anoxia (failure of
 the blood to transport adequate quantities of oxygen), stagnant anoxia (the
 slowing of the circulatory system), and histotoxic anoxia (the failure of
 respiratory enzymes to adequately function).
         Anoxia can occur temporarily during normal respiratory system regulation of
 changing cellular needs. An example of this would be climbing a flight of
 stairs. The increased oxygendemand of the cells in providing the mechanical
 energy required to climb ultimately produces a local hypoxia in the muscle
 cell. The first noticeable response to this external stress is usually an
 increase in breathing rate. This is called increased alveolar ventilation.
 The rate of our breathing is determined by the need for O2 in the cells and
 is the first response to hypoxic conditions.
 
 BODY RESPONSE TO ANOXIA
         If increases in the rate of alveolar respiration are insufficient to supply
 the oxygen needs of the cells the respiratory system responds by general
 vasodilation. This allows a greater flow of blood in the circulatory system.
 The sympathetic nervous system also acts to stimulate vasodilation within the
 skeletal muscle. At the level of the capillaries the normally closed
 precapillary sphincters open allowing a large flow of blood through the
 muscles. In turn the cardiac output increases both in terms of heart rate and
 stroke volume. The stroke volume, however, does not substantially increase in
 the non-athlete (Langley, et.al., 1980). This demonstrates an obvious benefit
 of regular exercise and physical conditioning particularly for an individual
 who will be exposed to high altitudes. The heart rate is increased by the
 action of the
 adrenal medulla which releases catecholamines. These catecholamines work
 directly on the myocardium to strengthen contraction. Another compensation
 mechanism is the release of renin by the kidneys. Renin leads to the
 production of angiotensin which serves to increase blood pressure (Langley,
 Telford, and Christensen, 1980). This helps to force more blood into
 capillaries. All of these changes are a regular and normal response of the
 body to external stressors. The question involved with altitude changes
 becomes what happens when the normal responses can no longer meet the oxygen
 demand from the cells?
 
 ACUTE MOUNTAIN SICKNESS
         One possibility is that Acute Mountain Sickness (AMS) may occur. AMS is
 common at high altitudes. At elevations over 10,000 feet, 75% of people will
 have mild symptoms (Princeton, 1995). The occurrence of AMS is dependent upon
 the elevation, the rate of ascent to that elevation, and individual
 susceptibility.
         Acute Mountain Sickness is labeled as mild, moderate, or severe dependent on
 the presenting symptoms. Many people will experience mild AMS during the
 process of acclimatization to a higher altitude. In this case symptoms of AMS
 would usually start 12-24 hours after arrival at a higher altitude and begin
 to decrease in severity about the third day. The symptoms of mild AMS are
 headache, dizziness, fatigue, shortness of breath, loss of appetite, nausea,
 disturbed sleep, and a general feeling of malaise (Princeton, 1995). These
 symptoms tend to increase at night when respiration is slowed during sleep.
 Mild AMS does not interfere with normal activity and symptoms generally
 subside spontaneously as the body acclimatizes to
 the higher elevation.
         Moderate AMS includes a severe headache that is not relieved by medication,
 nausea and vomiting, increasing weakness and fatigue, shortness of breath,
 and decreased coordination called  ataxia (Princeton, 1995). Normal activity
 becomes difficult at this stage of AMS, although the person may still be able
 to walk on their own.  A test for moderate AMS is to have the individual
 attempt to walk a straight line heel to toe. The person with ataxia will be
 unable to walk a straight line. If ataxia is indicated it is a clear sign
 that immediate descent is required. In the case of hiking or climbing it is
 important to get the affected individual to descend before the ataxia reaches
 the point where they can no longer walk on their own.
         Severe AMS presents all of the symptoms of mild and moderate AMS at an
 increased level of severity. In addition there is a marked shortness of
 breath at rest, the inability to walk, a decreasing mental clarity, and a
 potentially dangerous fluid buildup in the lungs.
 
 ACCLIMATIZATION
         There is really no cure for Acute Mountain Sickness other than
 acclimatization or
 descent to a lower altitude. Acclimatization is the process, over time, where
 the body adapts to the decrease in partial pressure of oxygen molecules at a
 higher altitude. The major cause of altitude illnesses is a rapid increase in
 elevation without an appropriate acclimatization period. The process of
 acclimatization generally takes 1-3 days at the new altitude. Acclimatization
 involves several changes in the structure and function of the body. Some of
 these changes happen immediately in response to reduced levels of oxygen
 while others are a slower adaptation. Some of the most significant changes
 are:
 
         Chemoreceptor mechanism increases the depth of alveolar ventilation. This
 allows for an increase in ventilation of about 60% (Guyton, 1969). This is an
 immediate response to oxygen debt. Over a period of several weeks the
 capacity to increase alveolar ventilation may increase 600-700%.
 
         Pressure in pulmonary arteries is increased, forcing blood into portions of
 the
 lung which are normally not used during sea level breathing.
 
         The body produces more red blood cells in the bone marrow to carry oxygen.
 This process may take several weeks. Persons who live at high altitude often
 have red blood cell counts 50% greater than normal.
 
         The body produces more of the enzyme 2,3-biphosphoglycerate that facilitates
 the release of oxygen from hemoglobin to the body tissues (Tortora, 1993).
 
 The acclimatization process is slowed by dehydration, over-exertion, alcohol
 and other depressant drug consumption. Longer term changes may include an
 increase in the size of the alveoli, and decrease in the thickness of the
 alveoli membranes. Both of these changes allow for more gas transfer.
 
 TREATMENT FOR AMS
         The symptoms of mild AMS can be treated with pain medications for headache.
 Some physicians recommend the medication Diamox (Acetazolamide). Both Diamox
 and headache medication appear to reduce the severity of symptoms, but do not
 cure the underlying problem of oxygen debt. Diamox, however, may allow the
 individual to metabolize more oxygen by breathing faster. This is especially
 helpful at night when respiratory drive is decreased. Since it takes a while
 for Diamox to have an effect, it is advisable to start taking it 24 hours
 before going to altitude. The recommendation of the Himalayan Rescue
 Association Medical Clinic is 125 mg.
 twice a day. The standard dose has been 250 mg., but their research shows no
 difference with the lower dose (Princeton, 1995). Possible side effects
 include tingling of the lips and finger tips, blurring of vision, and
 alteration of taste. These side effects may be reduced with the 125 mg. dose.
 Side effects subside when the drug is stopped. Diamox is a sulfonamide drug,
 so people who are allergic to sulfa drugs such as penicillin should not take
 Diamox. Diamox has also been known to cause severe allergic reactions to
 people with no previous history of Diamox or sulfa
 allergies. A trial course of the drug is usually conducted before going to a
 remote location where a severe allergic reaction could prove difficult to
 treat. Some recent data suggests that the medication Dexamethasone may have
 some effect in reducing the risk of mountain sickness when used in
 combination with Diamox (University of Iowa, 1995).
         Moderate AMS requires advanced medications or immediate descent to reverse
 the problem. Descending even a few hundred feet may help and definite
 improvement will be seen in descents of 1,000-2,000 feet. Twenty-four hours
 at the lower altitude will result in significant improvements. The person
 should remain at lower altitude until symptoms have subsided (up to 3 days).
 At this point, the person has become acclimatized to that altitude and can
 begin ascending again. Severe AMS requires immediate descent to lower
 altitudes (2,000 - 4,000 feet). Supplemental oxygen may be helpful in
 reducing the effects of altitude sicknesses but does not overcome all the
 difficulties that may result from the lowered barometric pressure.
 
 GAMOW BAG
         This invention has revolutionized field treatment of high altitude
 illnesses. The Gamow bag is basically a portable sealed chamber with a pump.
 The principle of operation is identical to the hyperbaric chambers used in
 deep sea diving. The person is placed inside the bag and it is inflated.
 Pumping the bag full of air effectively increases the concentration of oxygen
 molecules and therefore simulates a descent to lower altitude. In as little
 as 10 minutes the bag creates an atmosphere that corresponds to that at 3,000
 - 5,000 feet lower. After 1-2 hours in the bag, the
 person's body chemistry will have reset to the lower altitude. This lasts for
 up to 12 hours outside of the bag which should be enough time to travel to a
 lower altitude and allow for further acclimatization. The bag and pump weigh
 about 14 pounds and are now carried on most major high altitude expeditions.
 The gamow bag is particularly important where the possibility of immediate
 descent is not feasible.
 
 OTHER ALTITUDE-INDUCED ILLNESS
         There are two other severe forms of altitude illness. Both of these happen
 less
 frequently, especially to those who are properly acclimatized. When they do
 occur, it is usually the result of an increase in elevation that is too rapid
 for the body to adjust properly. For reasons not entirely understood, the
 lack of oxygen and reduced pressure often results in leakage of fluid through
 the capillary walls into either the lungs or the brain. Continuing to higher
 altitudes without proper acclimatization can lead to potentially serious,
 even life-threatening illnesses.
 
 HIGH ALTITUDE PULMONARY EDEMA (HAPE)
         High altitude pulmonary edema results from fluid buildup in the lungs. The
 fluid in the lungs interferes with effective oxygen exchange. As the
 condition becomes more severe, the level of oxygen in the bloodstream
 decreases, and this can lead to cyanosis, impaired cerebral function, and
 death. Symptoms include shortness of breath even at rest, tightness in the
 chest,
 marked fatigue, a feeling of impending suffocation at night, weakness, and a
 persistent productive cough bringing up white, watery, or frothy fluid
 (University of Iowa, 1995.). Confusion, and irrational behavior are signs
 that insufficient oxygen is reaching the brain. One of the methods for
 testing for HAPE is to check recovery time after exertion. Recovery time
 refers to the time after exertion that it takes for heart rate and
 respiration to return to near normal. An increase in this time may mean fluid
 is building up in the lungs. If a case of HAPE is suspected an immediate
 descent is a necessary life-saving measure (2,000 - 4,000 feet). Anyone
 suffering
 from HAPE must be evacuated to a medical facility for proper follow-up
 treatment. Early data suggests that nifedipine may have a protective effect
 against high altitude pulmonary edema (University of Iowa, 1995).
 
 HIGH ALTITUDE CEREBRAL EDEMA (HACE)
         High altitude cerebral edema results from the swelling of brain tissue from
 fluid leakage. Symptoms can include headache, loss of coordination (ataxia),
 weakness, and decreasing levels of consciousness including, disorientation,
 loss of memory, hallucinations, psychotic behavior, and coma. It generally
 occurs after a week or more at high altitude. Severe instances can lead to
 death if not treated quickly. Immediate descent is a necessary life-saving
 measure (2,000 - 4,000 feet).  Anyone suffering from HACE must be evacuated
 to a medical facility for proper follow-up
 treatment.
 
 CONCLUSION
         The importance of oxygen to the functioning of the human body is critical.
 Thus the effect of decreased partial pressure of oxygen at higher altitudes
 can be pronounced. Each individual adapts at a different speed to exposure to
 altitude and it is hard to know who may be affected by altitude sickness.
 There are no specific factors such as age, sex, or physical condition that
 correlate with susceptibility to altitude sickness. Most people can go up to
 8,000 feet with minimal effect. Acclimatization is often accompanied by fluid
 loss, so the ingestion of large amounts of fluid to remain properly hydrated
 is important (at least 3-4 quarts per day). Urine output should be copious
 and clear.
         From the available studies on the effect of altitude on the human body it
 would appear apparent that it is important to recognize symptoms early and
 take corrective measures. Light activity during the day is better than
 sleeping because respiration decreases during sleep, exacerbating the
 symptoms. The avoidance of tobacco, alcohol, and other depressant drugs
 including, barbiturates, tranquilizers, and sleeping pills is important.
 These depressants further decrease the respiratory drive during sleep
 resulting in a worsening of the symptoms. A high carbohydrate diet (more than
 70% of your calories from carbohydrates) while at altitude also
 appears to facilitate recovery.
         A little planning and awareness can greatly decrease the chances of altitude
 sickness. Recognizing early symptoms can result in the avoidance of more
 serious consequences of altitude sickness. The human body is a complex
 biochemical organism that requires an adequate supply of oxygen to function.
 The ability of this organism to adjust to a wide range of conditions is a
 testament to its survivability. The decreased partial pressure of oxygen with
 increasing
 altitude is one of these adaptations.
 
 
 Sources:
 Electric Differential Multimedia Lab, Travel Precautions and Advice,
 University of Iowa Medical College, 1995.
 
 Gerking, Shelby D., Biological Systems, W.B. Saunders Company, 1969.
 
 Grolier Electronic Publishing, The New Grolier Multimedia Encyclopedia, 1993.
 
 Grollman, Sigmund, The Human Body: Its Structure and Physiology, Macmillian
 Publishing Company, 1978.
 
 Guyton, Arthur C., Physiology of the Human Body, 5th Edition, Saunders
 College Publishing, 1979.
 
 Hackett, P., Mountain Sickness, The Mountaineers, Seattle, 1980.
 
 Hubble, Frank, High Altitude Illness, Wilderness Medicine Newsletter,
 March/April 1995.
 
 Hubble, Frank, The Use of Diamox in the Prevention of Acute Mountain
 Sickness, Wilderness Medicine Newsletter, March/April 1995.
 
 Isaac, J. and Goth, P., The Outward Bound Wilderness First Aid Handbook,
 Lyons & Burford, New  1991.
 
 Johnson, T., and Rock, P., Acute Mountain Sickness, New England Journal of
 Medicine, 1988:319:841-5
 
 Langley, Telford, and Christensen, Dynamic Anatomy and Physiology,
 McGraw-Hill, 1980.
 
 
 Princeton University, Outdoor Action Program, 1995.
 
 Starr, Cecie, and Taggart, Ralph, Biology: The Unity and Diversity of Life,
 Wadsworth Publishing Company, 1992.
 
 Tortora, Gerard J., and Grabowski, Sandra, Principles of Anatomy and
 Physiology, Seventh Edition, Harper Collins College Publishers, 1993.
 
 Wilkerson., J., Editor, Medicine for Mountaineering, Fourth Edition, The
 Mountaineers, Seattle, 1992.